Myelodysplastic syndrome - Knowledge (XXG)

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E, Hobbs GS, Hoffman R, Jabbour EJ, Kiladjian JJ, Larson RA, Le Beau MM, Loh ML, Löwenberg B, Macintyre E, Malcovati L, Mullighan CG, Niemeyer C, Odenike OM, Ogawa S, Orfao A, Papaemmanuil E, Passamonti F, Porkka K, Pui CH, Radich JP, Reiter A, Rozman M, Rudelius M, Savona MR, Schiffer CA, Schmitt-Graeff A, Shimamura A, Sierra J, Stock WA, Stone RM, Tallman MS, Thiele J, Tien HF, Tzankov A, Vannucchi AM, Vyas P, Wei AH, Weinberg OK, Wierzbowska A, Cazzola M, Döhner H, Tefferi A. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022 Sep 15;140(11):1200-1228. doi: 10.1182/blood.2022015850. PMID: 35767897; PMCID: PMC9479031.

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D, Ganster C, Ades L, Tobiasson M, Palomo L, Della Porta MG, Takaori-Kondo A, Ishikawa T, Chiba S, Kasahara S, Miyazaki Y, Viale A, Huberman K, Fenaux P, Belickova M, Savona MR, Klimek VM, Santos FPS, Boultwood J, Kotsianidis I, Santini V, Solé F, Platzbecker U, Heuser M, Valent P, Ohyashiki K, Finelli C, Voso MT, Shih LY, Fontenay M, Jansen JH, Cervera J, Gattermann N, Ebert BL, Bejar R, Malcovati L, Cazzola M, Ogawa S, Hellström-Lindberg E, Papaemmanuil E. Molecular International Prognostic Scoring System for Myelodysplastic Syndromes. NEJM Evid. 2022 Jul;1(7):EVIDoa2200008. doi: 10.1056/EVIDoa2200008. Epub 2022 Jun 12. PMID: 38319256.

53: 1619:, which are a major part of the supportive care for anemic MDS patients. Although the specific therapies patients receive may alleviate the RBC transfusion need in some cases, many MDS patients may not respond to these treatments, thus may develop secondary hemochromatosis due to iron overload from repeated RBC transfusions. Patients requiring relatively large numbers of RBC transfusions can experience the adverse effect of chronic iron overload on their liver, heart, and endocrine functions. 379: 1312:(WHO) modified this classification, introducing several new disease categories and eliminating others. In 2008, 2016, and 2022, the WHO developed new classification schemes that incorporated genetic findings (5q-) alongside morphology of the cells in the peripheral blood and bone marrow. As of 2024, the WHO 5th edition and International Consensus Classification (ICC) systems are both actively in use. 1607:, particularly in younger (i.e. less than 40 years of age) and more severely affected patients, offers the potential for curative therapy. The success of bone marrow transplantation has been found to correlate with severity of MDS as determined by the IPSS score, with patients having a more favorable IPSS score tend to have a more favorable outcome with transplantation. 3934: 1692:: Advanced age; severe neutropenia or thrombocytopenia; high blast count in the bone marrow (20–29%) or blasts in the blood; Auer rods; absence of ringed sideroblasts; abnormal localization or immature granulocyte precursors in bone marrow section; completely or mostly abnormal karyotypes, or complex marrow chromosome abnormalities and 565:, benzene, and certain chemotherapies; other risk factors have been inconsistently reported. Proving a connection between a suspected exposure and the development of MDS can be difficult, but the presence of genetic abnormalities may provide some supportive information. Secondary MDS can occur as a late 3436:

Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, Wang SA, Bagg A, Barbui T, Branford S, Bueso-Ramos CE, Cortes JE, Dal Cin P, DiNardo CD, Dombret H, Duncavage EJ, Ebert BL, Estey EH, Facchetti F, Foucar K, Gangat N, Gianelli U, Godley LA, Gökbuget N, Gotlib J, Hellström-Lindberg

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in 1997, then revised to IPSS-R and IPSS-M. This system takes into account the percentage of blasts in the marrow, cytogenetics, and number of cytopenias, as well as molecular features in the case of IPSS-M. Other prognostic tools include the 2007 WHO Prognostic Scoring System (WPSS), the MDA-LR (MD

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The best prognosis is seen with RA and RARS, where some nontransplant patients live more than a decade (typical is on the order of three to five years, although long-term remission is possible if a bone-marrow transplant is successful). The worst outlook is with RAEB-T, where the mean life expectancy

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and various international guidelines have recommended that chelation therapy be considered to decrease iron overload in selected MDS patients. Although deferasirox is generally well tolerated (other than episodes of gastrointestinal distress and kidney dysfunction in some patients), recently a safety

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are at risk of developing MDS. A link may exist between the development of MDS "in atomic-bomb survivors 40 to 60 years after radiation exposure" (in this case, referring to people who were in close proximity to the dropping of the atomic bombs in Hiroshima and Nagasaki during World War II). Children

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The IPSS-M incorporates 31 somatic genes in its risk stratification model. IPSS-M determined that multihit TP53 mutations, FLT3 mutations, and partial tandem duplication mutations of KMT2A (MLL) were strong predictors of adverse outcomes. Some SF3B1 mutations were associated with favorable outcomes,

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risk, and transfusion dependence respond best to lenalidomide. Typically, prognosis for these patients is favorable, with a 63-month median survival. Lenalidomide has dual action, by lowering the malignant clone number in patients with 5q-, and by inducing better differentiation of healthy erythroid

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Bernard E, Tuechler H, Greenberg PL, Hasserjian RP, Arango Ossa JE, Nannya Y, Devlin SM, Creignou M, Pinel P, Monnier L, Gundem G, Medina-Martinez JS, Domenico D, Jädersten M, Germing U, Sanz G, van de Loosdrecht AA, Kosmider O, Follo MY, Thol F, Zamora L, Pinheiro RF, Pellagatti A, Elias HK, Haase

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The exact number of people with MDS is not known because it can go undiagnosed and no tracking of the syndrome is mandated. Some estimates are on the order of 10,000 to 20,000 new cases each year in the United States alone. The number of new cases each year is probably increasing as the average age

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Since the early 20th century, some people with acute myelogenous leukemia were begun to be recognized to have a preceding period of anemia and abnormal blood cell production. These conditions were lumped together with other diseases under the term "refractory anemia". The first description of

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About seven per 100,000 people are affected by MDS; about four per 100,000 people newly acquire the condition each year. The typical age of onset is 70 years. The prognosis depends on the type of cells affected, the number of blasts in the bone marrow or blood, and the changes present in the

659:, MDS patients rarely experience injury from severe anemia. The two most serious complications in MDS patients resulting from their cytopenias are bleeding (due to lack of platelets) or infection (due to lack of white blood cells). Long-term transfusion of packed red blood cells leads to 4137:

Solé F, Espinet B, Sanz GF, Cervera J, Calasanz MJ, Luño E, et al. (February 2000). "Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Español de Citogenética Hematológica".

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The outlook in MDS is variable, with about 30% of patients progressing to refractory AML. The median survival time varies from years to months, depending on type. Stem-cell transplantation offers possible cure, with survival rates of 50% at 3 years, although older patients do poorly.

516:(therapeutic or accidental), or both (e.g., at the time of stem cell transplantation for another disease). Workers in some industries with heavy exposure to hydrocarbons such as the petroleum industry have a slightly higher risk of contracting the disease than the general population. 1284:, aminolevulinic acid enzyme deficiency and other more esoteric enzyme deficiencies are known to give a pseudomyelodysplastic picture in one of the cell lines; however, all three cell lines are never morphologically dysplastic in these entities with the exception of chloramphenicol, 890:. In consequence of these mutations, cellular levels of GATA2 are low and individuals develop over time hematological, immunological, lymphatic, or other presentations. Prominent among these presentations is MDS that often progresses to acute myelocytic leukemia, or less commonly, 1179:

or diffuse cytoplasmic staining) within erythroid precursors in the bone marrow aspirate (has no bearing on paraffin-fixed bone-marrow biopsy). Note: one can see PAS vacuolar positivity in L1 and L2 blasts (FAB classification; the L1 and L2 nomenclature is not used in the WHO

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in the liver and bone marrow. The disease is restricted to individuals with Down syndrome or genetic changes similar to those in Down syndrome, develops during pregnancy or shortly after birth, and resolves within 3 months, or in about 10% of cases, progresses to

1682:: Younger age; normal or moderately reduced neutrophil or platelet counts; low blast counts in the bone marrow (< 20%) and no blasts in the blood; no Auer rods; ringed sideroblasts; normal or mixed karyotypes without complex chromosome abnormalities; and 3541:

Wijermans P, Lübbert M, Verhoef G, Bosly A, Ravoet C, Andre M, et al. (March 2000). "Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients".

3295:/Mecham B, Drissi W, Brummell G, Dadi N, Martin DE. Severe B12 Deficiency Causing a Maturation Defect Mimicking Myelodysplastic Syndrome With Excess Blasts. Cureus. 2024 May 22;16(5):e60837. doi: 10.7759/cureus.60837. PMID: 38910768; PMCID: PMC11191413. 3613:

Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, et al. (May 2002). "Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B".

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have been conducted with iron chelating agents to address the question of whether iron chelation alters the natural history of patients with MDS who are transfusion dependent. Reversal of some of the consequences of iron overload in MDS by iron

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Lübbert M, Wijermans P, Kunzmann R, Verhoef G, Bosly A, Ravoet C, et al. (August 2001). "Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine".

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levels, number of RBC transfusions received, and associated organ dysfunction (heart, liver, and pancreas) should be monitored to determine iron levels. Monitoring serum ferritin may also be useful, aiming to decrease ferritin levels to

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The elimination of other causes of cytopenias, along with a dysplastic bone marrow, is required to diagnose a myelodysplastic syndrome, so differentiating MDS from other causes of anemia, thrombocytopenia, and leukopenia is important.

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Iwanaga M, Hsu WL, Soda M, Takasaki Y, Tawara M, Joh T, et al. (February 2011). "Risk of myelodysplastic syndromes in people exposed to ionizing radiation: a retrospective cohort study of Nagasaki atomic bomb survivors".

1248:. This morphology can be difficult to differentiate from treated leukemia and recovering immature normal marrow elements. Also, topographic alteration of the nucleated erythroid cells can be seen in early myelodysplasia ( 4084:

Parisi S, Finelli C. Prognostic Factors and Clinical Considerations for Iron Chelation Therapy in Myelodysplastic Syndrome Patients. J Blood Med. 2021 Dec 3;12:1019-1030. doi: 10.2147/JBM.S287876. PMID: 34887690; PMCID:

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also characterized by less than 5% myeloblasts in the bone marrow, but distinguished by the presence of 15% or greater of red cell precursors in the marrow being abnormal iron-stuffed cells called "ringed sideroblasts"

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function over time leads to the accumulation of DNA mutations in hematopoietic stem cells, and this accounts for the increased incidence of MDS in older patients. Researchers point to the accumulation of mitochondrial

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DeZern AE, Malcovati L, Ebert BL. CHIP, CCUS, and Other Acronyms: Definition, Implications, and Impact on Practice. Am Soc Clin Oncol Educ Book. 2019 Jan;39:400-410. doi: 10.1200/EDBK_239083. Epub 2019 May 17. PMID:

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Hypoplastic MDS, MDS with fibrosis, MDS with bi-allelic TP53 inactivation, and CCUS were added to the WHO 5th ed. Another subtype called Myeloid neoplasms with germ line predisposition and organ dysfunction includes

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Molenaar RJ, Radivoyevitch T, Maciejewski JP, van Noorden CJ, Bleeker FE (December 2014). "The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation".

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The early identification, characterization and classification of this disorder were problematical, and the syndrome went by many names until the 1976 FAB classification was published and popularized the term MDS.

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Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. (August 1976). "Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group".

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5-azacytidine and decitabine has been shown to decrease blood transfusion requirements and to retard the progression of MDS to AML. Lenalidomide was approved by the FDA in December 2005 only for use in the

484:, but at least half the patients are asymptomatic and their MDS is discovered only incidentally on routine blood counts. Previous chemotherapy or radiation exposure is an important factor in the person's 4221:

DeZern AE, Greenberg PL. The trajectory of prognostication and risk stratification for patients with myelodysplastic syndromes. Blood. 2023 Dec 28;142(26):2258-2267. doi: 10.1182/blood.2023020081. PMID:

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Luo T, Zurko J, Astle J, Shah NN. Mimicking Myelodysplastic Syndrome: Importance of Differential Diagnosis. Case Rep Hematol. 2021 Nov 29;2021:9661765. doi: 10.1155/2021/9661765. PMID: 34881068; PMCID:

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cell death occurs in bone-marrow cells. Clonal expansion of the abnormal cells results in the production of cells that have lost the ability to differentiate. If the overall percentage of bone-marrow

4038:"The impact of intensive antileukaemic treatment strategies on prognosis of myelodysplastic syndrome patients aged less than 61 years according to International Prognostic Scoring System risk groups" 1658:

has been shown. Iron overload not only leads to organ damage, but also induces genomic instability and modifies the hematopoietic niche, favoring progression to acute leukemia. The MDS Foundation,

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should not be overlooked, as it can morphologically resemble MDS in bone-marrow biopsies. Risk factors for copper deficiency include bariatric surgery, zinc supplementation, and celiac disease.

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The typical age at diagnosis of MDS is between 60 and 75 years; a few people are younger than 50, and diagnoses are rare in children. Males are slightly more commonly affected than females.

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Hellström-Lindberg ES, Kröger N. Clinical decision-making and treatment of myelodysplastic syndromes. Blood. 2023 Dec 28;142(26):2268-2281. doi: 10.1182/blood.2023020079. PMID: 37874917.

3469:"A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome" 2535:

Hall T, Gurbuxani S, Crispino JD. Malignant progression of preleukemic disorders. Blood. 2024 May 30;143(22):2245-2255. doi: 10.1182/blood.2023020817. PMID: 38498034; PMCID: PMC11181356.

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MDS may present with isolated neutropenia or thrombocytopenia without anemia and with dysplastic changes confined to the single lineage. This is called MDS-Low Blasts in the WHO 5th ed.

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of the affected cells. The average survival time following diagnosis is 2.5 years. MDS was first recognized in the early 1900s; it came to be called myelodysplastic syndrome in 1976.

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Takasaki K, Chou ST. GATA1 in Normal and Pathologic Megakaryopoiesis and Platelet Development. Adv Exp Med Biol. 2024;1459:261-287. doi: 10.1007/978-3-031-62731-6_12. PMID: 39017848.

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Hasserjian RP, Germing U, Malcovati L. Diagnosis and classification of myelodysplastic syndromes. Blood. 2023 Dec 28;142(26):2247-2257. doi: 10.1182/blood.2023020078. PMID: 37774372.

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or liver failure occurred, some resulting in death. Due to this, patients should be closely monitored on deferasirox therapy prior to the start of therapy and regularly thereafter.

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Jankowska AM, Gondek LP, Szpurka H, Nearman ZP, Tiu RV, Maciejewski JP (March 2008). "Base excision repair dysfunction in a subgroup of patients with myelodysplastic syndrome".

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Most cases of unclassifiable MDS from the 2008 WHO version would be considered Clonal Cytopenias of Undetermined Significance (CCUS) by the WHO 5th ed. CCUS is defined as:

473:, a significant proportion of deaths occur as a result of bleeding or infection. Leukemia that occurs as a result of myelodysplasia is notoriously resistant to treatment. 4232:

Aul C, Giagounidis A, Germing U (June 2001). "Epidemiological features of myelodysplastic syndromes: results from regional cancer surveys and hospital-based statistics".

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is critical in the regulation of proliferation genes, and the loss of DNA methylation control can lead to uncontrolled cell growth and cytopenias. The recently approved

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Fenaux P, Haase D, Sanz GF, Santini V, Buske C (September 2014). "Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up".

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Van den Berghe H, Cassiman JJ, David G, Fryns JP, Michaux JL, Sokal G (October 1974). "Distinct haematological disorder with deletion of long arm of no. 5 chromosome".

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All of these conditions are characterized by abnormalities in the production of one or more of the cellular components of blood (red cells, white cells other than

4932: 4833: 1240:, which are islands of immature precursors cells (myeloblasts and promyelocytes) localized to the center of the intertrabecular space rather than adjacent to the 1048:

from disrupted DNA. Virtual karyotyping does not require cell culture and has a dramatically higher resolution than conventional cytogenetics, but cannot detect

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One or more somatic mutations otherwise found in patients with myeloid neoplasms detected in bone marrow or peripheral blood cells with an allele burden of ≥ 2%

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is less than one year. About one-quarter of patients develop overt leukemia. The others die of complications of low blood count or unrelated diseases. The

1362: 1349: 3651:"Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B" 2435:

Myelodysplastic syndromes (MDS) occurring in Agent Orange exposed individuals carry a mutational spectrum similar to that of de novo MDS - PMC (nih.gov)

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was published in 1976, and revised in 1982. It was used by pathologists and clinicians for almost 20 years. Cases were classified into five categories:

488:. Fever, weight loss and splenomegaly should point to a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) rather than pure myelodysplastic process. 4398: 651:

attributable to MDS results not from transformation to AML, but rather from the cytopenias seen in all MDS patients. While anemia is the most common

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Mutations in splicing factors have been found in 40–80% of people with MDS, with a higher incidence of mutations detected in people who have more

790: 331: 3790:"Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia" 1784:

In 1974 and 1975, a group of pathologists from France, the US, and Britain produced the first widely used classification of these diseases. This

1590:. In the United States, treatment of MDS with lenalidomide costs about $ 9,200 per month. The chemotherapy may be supported by other drugs like 1785: 1759:

of the population increases, and some authors propose that the number of new cases in those over 70 may be as high as 15 per 100,000 per year.

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warning by the FDA and Novartis was added to deferasirox treatment guidelines. Following postmarketing use of deferasirox, rare cases of acute

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for oral use. These options now provide potentially useful drugs for treating the iron overload problem. A third chelating agent is available,

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Typically seen in older women with normal or high platelet counts and isolated deletions of the long arm of chromosome 5 in bone marrow cells.

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do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include

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Anderson Lower-Risk MDS Prognostic Scoring System), EuroMDS, and Cleveland Clinic Foundation/Munich Leukemia Laboratory scoring systems.

1520:) as well as help determine the best timing of this therapy. Supportive care with blood products and hematopoietic growth factors (e.g. 1080:

Dysplasia can affect all three lineages seen in the bone marrow. The best way to diagnose dysplasia is by morphology and special stains (

5264: 3692:"Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome" 1269: 1158: 1013:: This is required to establish the diagnosis since all hematopathologists consider dysplastic marrow the key feature of myelodysplasia. 833:) occur in 10–20% of patients with myelodysplastic syndrome, and confer a worsened prognosis in low-risk MDS. Because the incidence of 5476: 1031: 585:

occurs after a shorter latency of only 1–3 years and can have a 11q23 translocation. Other pre-existing bone-marrow disorders such as

323:. The different types of MDS are identified based on the specific characteristics of the changes in the blood cells and bone marrow. 3987:

Küley-Bagheri Y, Kreuzer KA, Monsef I, Lübbert M, Skoetz N, et al. (Cochrane Haematological Malignancies Group) (August 2018).

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MDS most often develops without an identifiable cause. Risk factors include exposure to an agent known to cause DNA damage, such as

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The goals of therapy are to control symptoms, improve quality of life, improve overall survival, and decrease progression to AML.

749:. An emerging perspective is that the underlying mechanism of MDS could be a defect in one or more pathways that are involved in 4989: 4750: 4372: 746: 5254: 5165: 4994: 4551: 1885: 1528: 915: 891: 700: 1376:

Includes the subset Refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). Revised to MDS with LB.

5338: 1551:: Complete response rate reported as high as 43%. A phase I study has shown efficacy in AML when decitabine is combined with 439:

Many individuals are asymptomatic, and blood cytopenia or other problems are identified as a part of a routine blood count:

1524:) is the mainstay of therapy. The regulatory environment for the use of erythropoietins is evolving, according to a recent 5106: 4967: 4865: 1230: 1561:: Effective in reducing red blood cell transfusion requirement in patients with the chromosome 5q deletion subtype of MDS 1226: 581:, typically occurs 3–7 years after exposure and frequently demonstrates loss of chromosome 5 or 7. MDS after exposure to 5446: 5381: 4917: 4843: 3917: 1889: 1535: 1038:, offers rapid detection of several chromosome abnormalities associated with MDS, including del 5q, −7, +8, and del 20q. 5431: 5212: 5148: 5096: 5084: 4855: 4823: 4743: 2026: 1341: 1216: 2389:"Evidence-Based Minireview: Myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes: a focused review" 4354: 476:

Anemia dominates the early course. Most symptomatic patients complain of the gradual onset of fatigue and weakness,

5471: 5343: 5110: 1979: 1081: 625: 470: 3063:"Clinical and biological implications of ancestral and non-ancestral IDH1 and IDH2 mutations in myeloid neoplasms" 2303:

Myelodysplastic Syndrome. The Leukemia & Lymphoma Society. White Plains, NY. 2001. p 24. Retrieved 05–12–2008.

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RAEB was divided into RAEB-I (5–9% blasts) and RAEB-II (10–19%) blasts, which has a poorer prognosis than RAEB-I.

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Seewald L, Taub JW, Maloney KW, McCabe ER (September 2012). "Acute leukemias in children with Down syndrome".

2716:"Potential relationship between inadequate response to DNA damage and development of myelodysplastic syndrome" 1252:

and RARS), where normoblasts are seen next to bony trabeculae instead of forming normal interstitially placed

1103: 1084:) used on the bone marrow aspirate and peripheral blood smear. Dysplasia in the myeloid series is defined by: 68: 382:

Enlarged spleen due to myelodysplastic syndrome; CT scan coronal section, spleen in red, left kidney in green

4927: 3741:"Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study" 1597: 1591: 1571:

for the treatment of adults with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).

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aberrations leading to the suggestion that MDS is, in part, related to an inability to adequately cope with

738: 704: 601: 582: 5404: 5190: 5074: 5039: 4957: 4890: 4813: 4723: 1872: 1568: 1517: 1337: 1128: 1049: 789:, and in December 2005, the US FDA approved the drug for this indication. Patients with isolated 5q-, low 754: 458: 351: 269: 206: 5441: 3331:"Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML" 2046: 1956: 996: 3649:

Silverman LR, McKenzie DR, Peterson BL, Holland JF, Backstrom JT, Beach CL, et al. (August 2006).

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Myelodysplasia is a diagnosis of exclusion and must be made after proper determination of iron stores,

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has been known to be associated with dysplastic abnormalities of hematopoietic stem cells. By 2005,

762: 538: 2076: 1531:. However, no comment on the use of hematopoietic growth factors for MDS was made in that document. 4636: 3690:

Kantarjian HM, O'Brien S, Shan J, Aribi A, Garcia-Manero G, Jabbour E, et al. (January 2007).

1928: 1114: 1059: 957: 253: 110: 3831:"Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia" 3739:

Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, et al. (April 2006).

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Oosterveld M, Wittebol SH, Lemmens WA, Kiemeney BA, Catik A, Muus P, et al. (October 2003).

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Molenaar RJ, Thota S, Nagata Y, Patel B, Clemente M, Przychodzen B, et al. (November 2015).

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Cazzola M, Invernizzi R, Bergamaschi G, Levi S, Corsi B, Travaglino E, et al. (March 2003).

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Cytogenetic abnormalities can be detected by conventional cytogenetics, a FISH panel for MDS, or

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Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O'Brien S, Cortes J, et al. (January 2007).

4475: 4113: 2338: 2224: 378: 5358: 5313: 5222: 4669: 4588: 4448: 4328: 4292: 4249: 4204: 4155: 4117: 4059: 4018: 3969: 3893: 3852: 3811: 3762: 3713: 3672: 3631: 3595: 3559: 3490: 3401: 3360: 3278: 3243: 3185: 3144: 3092: 3038: 3002: 2953: 2904: 2861: 2834: 2796: 2747: 2688: 2667:"Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia" 2647: 2601: 2566: 2515: 2463: 2418: 2230: 2202: 1812: 1717: 1655: 1249: 1145: 1074: 1073:

The features generally used to define an MDS are blood cytopenias, ineffective hematopoiesis,

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is helpful to identify blasts, abnormal myeloid maturation, and establish the presence of any

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mutations increases as the disease malignancy increases, these findings together suggest that

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counts. Some types of MDS cause an increase in the production of immature blood cells (called

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Some people have a history of exposure to chemotherapy (especially alkylating agents such as

4578: 4570: 4320: 4284: 4241: 4194: 4147: 4105: 4049: 4008: 4000: 3883: 3842: 3801: 3752: 3703: 3662: 3623: 3587: 3551: 3480: 3391: 3350: 3342: 3270: 3233: 3225: 3175: 3134: 3126: 3082: 3074: 3030: 2992: 2984: 2943: 2896: 2826: 2786: 2778: 2737: 2727: 2678: 2637: 2558: 2505: 2497: 2455: 2408: 2400: 2192: 2184: 1906: 1647:, but it has limited utility in MDS patients because of a major side effect of neutropenia. 1285: 1000: 992: 946: 942: 934: 883: 765:

pathway that is involved in handling oxidative DNA damages may be defective in these cases.

546: 501: 413: 320: 312: 308: 4735: 3870:

List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. (October 2006).

1023:. Conventional cytogenetics require a fresh specimen since live cells are induced to enter 866:

mutations cause a reduction in the cellular levels of the gene's product, GATA2. The GATA2

703:

take advantage of this mechanism by creating a more orderly DNA methylation profile in the

632:

in which a series of mutations occurs in an initially normal cell and transforms it into a

5419: 4541: 3516: 1918: 1822:) in the bone marrow and pathological abnormalities primarily seen in red cell precursors 1650: 1582: 1277: 1035: 696: 640: 525: 485: 327: 186: 1577:

is licensed for MDS-RS (Ring Sideroblasts) and other low- and intermediate-risk subtypes.

1268:

deficiencies, and nutrient deficiencies are ruled out. Also, congenital diseases such as

841:

mutations are important drivers of progression of MDS to a more malignant disease state.

17: 3912:"FDA Approves New Therapy for Myelodysplastic Syndromes (MDS) That Can Be Taken at Home" 3829:

Blum W, Klisovic RB, Hackanson B, Liu Z, Liu S, Devine H, et al. (September 2007).

3467:

Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Pérez WS, Anasetti C, et al. (July 2004).

2892: 1728:

is the most commonly used tool for determining the prognosis of MDS, first published in

4652: 4324: 4013: 3988: 3355: 3330: 3238: 3213: 3139: 3114: 3087: 3062: 2997: 2972: 2930:

List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, et al. (February 2005).

2791: 2766: 2742: 2715: 2510: 2485: 2413: 2197: 2172: 1974: 1880: 1860: 1844: 1827: 1807: 1664: 1623: 1521: 1443: 1055: 980: 910: 761:

were found in the DNA of a significant proportion of MDS patients, indicating that the

711: 628:(AML) is said to have occurred. The progression of MDS to AML is a good example of the 590: 542: 394: 72: 4641: 2313: 1895:

characterized by less than 20% myeloblasts in the bone marrow and greater than 1*10/L

1202:

Hyposegmented nuclear features in platelet producing megakaryocytes (lack of lobation)

569:

of cancer therapy (therapy associated MDS, t-MDS). MDS after exposure to radiation or

5465: 5014: 4946: 4536: 4288: 4151: 4106: 4054: 4037: 3938: 3591: 2254: 1552: 1542: 1210: 984: 875: 718: 680: 679:

structure in MDS has explained the success of two (namely the hypomethylating agents

660: 534: 284: 147: 4261: 4183:"International scoring system for evaluating prognosis in myelodysplastic syndromes" 4181:

Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. (March 1997).

4167: 4071: 3725: 3502: 3413: 3329:

Gondek LP, Tiu R, O'Keefe CL, Sekeres MA, Theil KS, Maciejewski JP (February 2008).

2578: 905:, renamed Transient Abnormal Myelopoiesis (TAM), is the abnormal proliferation of a 604:, but the specific defects responsible for these diseases remain poorly understood. 5329: 5318: 4709: 4340: 4004: 3774: 2916: 2700: 1997: 1991: 1636: 1616: 1587: 1574: 1558: 1439: 1395: 1315:

The list of dysplastic syndromes under the 2008 WHO system included the following:

1190:

iron stain (>15% ringed sideroblasts when counted among red cell precursors for

1149: 1016: 849:

GATA2 deficiency is a group of disorders caused by a defect, familial, or sporadic

786: 782: 778: 774: 758: 707: 688: 578: 529: 509: 450: 446: 401:) – chronic tiredness, shortness of breath, chilled sensation, sometimes chest pain 359: 347: 276: 202: 139: 4275:

Block M, Jacobson LO, Bethard WF (July 1953). "Preleukemic acute human leukemia".

3378:

Huff JD, Keung YK, Thakuri M, Beaty MW, Hurd DD, Owen J, et al. (July 2007).

2404: 386:

Signs and symptoms are nonspecific and generally related to the blood cytopenias:

4663: 3806: 3789: 3346: 3130: 2988: 2782: 2767:"Myelodysplastic syndrome: an inability to appropriately respond to damaged DNA?" 2642: 2625: 2501: 2279: 5298: 4784: 3274: 3034: 2714:

Zhou T, Chen P, Gu J, Bishop AJ, Scott LM, Hasty P, et al. (January 2015).

2388: 1968: 1944: 1939: 1819: 1644: 1640: 965: 742: 710:, thereby restoring normal blood counts and retarding the progression of MDS to 639:

Although recognition of leukemic transformation was historically important (see

574: 404: 355: 245: 210: 133: 60: 4712: 3485: 3468: 2683: 2666: 2593: 2562: 1871:

characterized by 5–19% myeloblasts in the marrow (>20% blasts is defined as

1742:

whereas certain genetic subsets of SF3B1 mutations were not. In low-risk MDS,

1465:

Persistent cytopenia (≥ 4 months) in one or more peripheral blood cell lineages

1186:(10 or more iron granules encircling one-third or more of the nucleus) seen on 537:

are susceptible to MDS, and a family history may indicate a hereditary form of

4674: 3555: 3229: 3180: 3163: 2188: 1985: 1962: 1950: 1933: 1601: 1548: 1292: 1236:

On the bone-marrow biopsy, high-grade dysplasia (RAEB-I and RAEB-II) may show

1206: 1169: 1165: 1135: 1092: 938: 750: 684: 672: 613: 608:

of blood precursor cells is impaired, and a significant increase in levels of

425: 421: 398: 367: 343: 316: 288: 265: 241: 197: 151: 118: 89: 64: 4199: 4182: 3847: 3830: 3667: 3650: 2459: 469:

Although patients with MDS have an overall risk of almost 30% for developing

4802: 4704: 4680: 4626: 4574: 3627: 2546: 2002: 1896: 1632: 1330: 1308:

In the late 1990s, a group of pathologists and clinicians working under the

1245: 1241: 1045: 1024: 961: 887: 652: 644: 609: 562: 513: 497: 408: 217: 4592: 4399:"Panama says President Cortizo still in remission from rare blood disorder" 4296: 4253: 4159: 4063: 4022: 3973: 3897: 3856: 3815: 3766: 3717: 3676: 3635: 3599: 3563: 3494: 3405: 3364: 3282: 3247: 3189: 3148: 3096: 3042: 3006: 2973:"The significance of spliceosome mutations in chronic lymphocytic leukemia" 2957: 2838: 2830: 2800: 2751: 2692: 2651: 2605: 2570: 2519: 2467: 2422: 2206: 1446:

instead of the usual cytopenia. This may represent overlap syndromes with

741:

aging is thought to be associated with the accrual of multiple genetic and

4208: 3872:"Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion" 2908: 2865: 5287: 5028: 4879: 4718: 4332: 4104:

Kasper, Dennis L, Braunwald, Eugene, Fauci, Anthony, et al. (2005).

3888: 3871: 2948: 2931: 2765:

Zhou T, Hasty P, Walter CA, Bishop AJ, Scott LM, Rebel VI (August 2013).

2732: 2015: 1408:

Seen in those cases of megakaryocyte dysplasia with fibrosis and others.

1120: 950: 597: 566: 505: 433: 417: 114: 93: 4583: 3078: 5137: 5063: 4766: 4245: 3757: 3740: 3708: 3691: 1265: 1176: 976: 867: 521: 477: 429: 303:. Problems with blood cell formation result in some combination of low 292: 249: 155: 4609: 3396: 3379: 5244: 4793: 4778: 4621: 4555: 3214:"Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update" 3212:

Bhatnagar N, Nizery L, Tunstall O, Vyas P, Roberts I (October 2016).

2900: 1712:

Poor: complex (>3 chromosomal aberrations); chromosome 7 anomalies

1513: 1044:

can be done for MDS, which uses computational tools to construct the

972: 633: 517: 481: 390: 304: 261: 237: 76: 1304:

World Health Organization and International Consensus Classification

1077:, dysgranulopoiesis, dysmegakaropoiesis, and increased myeloblasts. 757:

indicates defects in DNA repair processes. Also elevated levels of

956:

Blood tests to eliminate other common causes of cytopenias such as

553:/9L syndromes each account for about 15% of MDS cases in children. 5179: 4685: 3960:"Lenalidomide (Revlimid) for anemia of myelodysplastic syndrome". 3162:

Hirabayashi S, Wlodarski MW, Kozyra E, Niemeyer CM (August 2017).

1899:(a type of white blood cell) circulating in the peripheral blood. 1794: 1771:"preleukemia" as a specific entity was published in 1953 by Block 1498: 1494: 1490: 1486: 1482: 1356: 879: 855: 648: 550: 377: 3937:

This article incorporates text from this source, which is in the

1157:

Erythroid nuclear strings or internuclear bridging (also seen in

1134:

Dimorphic granules (basophilic and eosinophilic granules) within

621: 2173:"Myelodysplastic syndromes: diagnosis, prognosis, and treatment" 859: 723: 300: 163: 4739: 1471:

All other causes of cytopenia and molecular aberration excluded

4355:"Table 1: French-American-British (FAB) Classification of MDS" 2852:

Bunn HF (November 1986). "5q- and disordered haematopoiesis".

2139:"Myelodysplastic Syndromes Treatment (PDQ®) – Patient Version" 1709:

Intermediate or variable: +8, other single or double anomalies

1229:

positivity) in eosinophils is a marker of abnormality seen in

988: 785:

drug, was recognized to be effective in MDS patients with the

676: 1389:

Revised to MDS with IB1 and MDS with IB2. (Increased Blasts)

5349:

Adult type of generalized eruption of cutaneous mastocytosis

1295:, and platelets or their progenitor cells, megakaryocytes). 63:

from a person with myelodysplastic syndrome. A hypogranular

455:

Abnormal granules in cells, abnormal nuclear shape and size

2547:"What biologic factors predict for transformation to AML?" 2171:

Germing U, Kobbe G, Haas R, Gattermann N (November 2013).

1019:

or chromosomal studies: This is ideally performed on the

1615:

Iron overload can develop in MDS as a result of the RBC

1034:

testing, usually ordered together with conventional cyto

3023:

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

2932:"Efficacy of lenalidomide in myelodysplastic syndromes" 1866:

Refractory anemia with excess blasts in transformation

1594:(ATRA), however the evidence of benefit is not clear. 1818:

characterized by less than 5% primitive blood cells (

1468:

Diagnostic criteria of myeloid neoplasm not fulfilled

773:

Since at least 1974, the deletion in the long arm of

691:) commercially available medications approved by the 407:(low neutrophil count) – increased susceptibility to 340:

medications to increase the making of red blood cells

4599: 3380:"Copper deficiency causes reversible myelodysplasia" 1199:

Megakaryocytic series (can be the most subjective):

941:: The blood film morphology can provide clues about 524:

exposures have been associated with myelodysplasia.

5428: 5401: 5394: 5372: 5327: 5295: 5286: 5231: 5209: 5187: 5178: 5145: 5136: 5127: 5093: 5071: 5062: 5036: 5027: 5007: 4976: 4954: 4945: 4914: 4887: 4878: 4852: 4810: 4801: 4792: 4777: 4695: 4603: 4444:"Paul Motian dies at 80; jazz drummer and composer" 1696:bone marrow culture with a leukemic growth pattern 416:(low platelet count) – increased susceptibility to 216: 196: 182: 169: 132: 124: 99: 83: 42: 37: 3164:"Heterogeneity of GATA2-related myeloid neoplasms" 2551:Best Practice & Research. Clinical Haematology 2479: 2477: 1855:characterized by 5–19% myeloblasts in the marrow 1750:mutations are associated with worsened survival. 1686:marrow culture with a nonleukemic growth pattern 1355:Revised to MDS with LB and RS or MDS with LB and 1280:– vacuolization in all cell lines may be seen in 730:as evidence of mitochondrial dysfunction in MDS. 655:in MDS patients, given the ready availability of 362:followed by a stem-cell transplant from a donor. 5270:Refractory cytopenia with multilineage dysplasia 4425:"Veteran actor Pat Hingle dies at 84 in NC home" 4112:(16th ed.). New York: McGraw-Hill. p. 2812: 2810: 2531: 2529: 2373: 2371: 2369: 2367: 2365: 2363: 2361: 2359: 1371:Refractory cytopenia with multilineage dysplasia 1225:Other stains can help in special cases (PAS and 945:, clumping of the platelets leading to spurious 794:cells, as seen in patients without 5q deletion. 3108: 3106: 2600:, Treasure Island (FL): StatPearls Publishing, 2081:NORD (National Organization for Rare Disorders) 1905:(A table comparing these is available from the 1361:Includes the subset Thrombocytosis (MDS/MPN-T) 4933:Accelerated phase chronic myelogenous leukemia 3517:"Centers for Medicare & Medicaid Services" 3115:"GATA factor mutations in hematologic disease" 1622:For patients requiring many RBC transfusions, 617: 4751: 2971:Rozovski U, Keating M, Estrov Z (July 2013). 1516:patients for more aggressive treatment (i.e. 1003:should be considered for all anemic patients. 930:A typical diagnostic investigation includes: 8: 3962:The Medical Letter on Drugs and Therapeutics 3306:"Rudhiram Hematology Clinic - Google Search" 2626:"How I treat mixed-phenotype acute leukemia" 1780:French-American-British (FAB) classification 1438:Patients with MDS occasionally present with 1238:atypical localization of immature precursors 717:Some authors have proposed that the loss of 4277:Journal of the American Medical Association 3993:The Cochrane Database of Systematic Reviews 1363:myelodysplastic/myeloproliferative disorder 346:. Drug therapy may include the medications 27:Diverse collection of blood-related cancers 5398: 5292: 5184: 5142: 5133: 5068: 5033: 4951: 4884: 4807: 4798: 4789: 4758: 4744: 4736: 4600: 4108:Harrison's Principles of Internal Medicine 2133: 2131: 2129: 2127: 2125: 2123: 2121: 2119: 2117: 1350:Refractory anemia with ringed sideroblasts 589:following immunosuppressive treatment and 51: 34: 4582: 4198: 4053: 4012: 3887: 3846: 3805: 3756: 3707: 3666: 3484: 3395: 3354: 3237: 3179: 3138: 3086: 2996: 2947: 2790: 2741: 2731: 2682: 2641: 2509: 2486:"Inherited bone marrow failure syndromes" 2412: 2218: 2216: 2196: 2166: 2164: 2162: 2160: 2115: 2113: 2111: 2109: 2107: 2105: 2103: 2101: 2099: 2097: 1324:Description and WHO 5th ed. counterparts 1274:Pearson's syndrome (sideroblastic anemia) 1272:(CDA I through IV) have been recognized, 443:Neutropenia, anemia, and thrombocytopenia 4545:) is being considered for deletion. See 2229:(8th ed.). PMPH-USA. p. 1544. 1833:Refractory anemia with ring sideroblasts 1790: 1317: 1192:refractory anemia with ring sideroblasts 616:rises over a particular cutoff (20% for 283:, exposure to certain chemicals such as 5250:Refractory anemia with excess of blasts 2038: 1726:International Prognostic Scoring System 1344:. Revised to MDS with LB (low blasts) 1215:Ballooning of the platelets (seen with 332:hematopoietic stem cell transplantation 295:, and exposure to heavy metals such as 3218:Current Hematologic Malignancy Reports 3113:Crispino JD, Horwitz MS (April 2017). 2018:– type of tumor made of leukemic cells 1786:French-American-British classification 1534:Agents have been approved by the U.S. 3056: 3054: 3052: 2141:. NCI. 12 August 2015. Archived from 1660:National Comprehensive Cancer Network 7: 5415:Acute panmyelosis with myelofibrosis 2343:The Lecturio Medical Concept Library 2318:The Lecturio Medical Concept Library 2284:The Lecturio Medical Concept Library 2259:The Lecturio Medical Concept Library 2057:from the original on 27 October 2016 1850:Refractory anemia with excess blasts 1382:Refractory anemia with excess blasts 1159:congenital dyserythropoietic anemias 903:Transient myeloproliferative disease 898:Transient myeloproliferative disease 878:, maintenance, and functionality of 821:Mutations in the genes encoding for 753:. In MDS an increased frequency of 424:(bruising), as well as subcutaneous 75:, in part related to removal of the 5265:Paroxysmal nocturnal hemoglobinuria 4373:"Saxophonist Brecker dies from MDS" 4234:International Journal of Hematology 3876:The New England Journal of Medicine 3168:International Journal of Hematology 2936:The New England Journal of Medicine 2484:Dokal I, Vulliamy T (August 2010). 1706:Good: normal, -Y, del(5q), del(20q) 1270:congenital dyserythropoietic anemia 1227:naphthol ASD chloroacetate esterase 643:), a significant proportion of the 4486:from the original on 12 March 2017 4325:10.1111/j.1365-2141.1976.tb03563.x 2387:Patnaik MM, Lasho T (2020-12-04). 2177:Deutsches Ärzteblatt International 1032:fluorescence in situ hybridization 630:multistep theory of carcinogenesis 25: 4549:to help reach a consensus. › 4442:McClellan D (November 24, 2011). 3263:Molecular Genetics and Metabolism 1512:The IPSS scoring system can help 1426:MDS with single lineage dysplasia 1414:Refractory cytopenia of childhood 693:U.S. Food and Drug Administration 602:multipotent bone-marrow stem cell 73:abnormally shaped red blood cells 4990:Juvenile myelomonocytic leukemia 4361:from the original on 2006-01-17. 4289:10.1001/jama.1953.03690110032010 4152:10.1046/j.1365-2141.2000.01868.x 4055:10.1046/j.1365-2141.2003.04544.x 3932: 3592:10.1111/j.1365-2141.2001.02933.x 2243:from the original on 2016-10-27. 1888:(CMML), not to be confused with 1538:(FDA) for the treatment of MDS: 1217:interference contrast microscopy 1027:to allow chromosomes to be seen. 701:DNA methyltransferase inhibitors 5255:Chromosome 5q deletion syndrome 5166:Acute megakaryoblastic leukemia 4995:Chronic myelomonocytic leukemia 4906:Myeloid dendritic cell leukemia 4506:"Illness as More Than Metaphor" 3523:from the original on 2008-10-05 1886:Chronic myelomonocytic leukemia 1529:National coverage determination 1434:MDS with increased blood counts 916:acute megakaryoblastic leukemia 892:chronic myelomonocytic leukemia 583:DNA topoisomerase II inhibitors 222:Typical survival time 2.5 years 5339:Diffuse cutaneous mastocytosis 4313:British Journal of Haematology 4140:British Journal of Haematology 4042:British Journal of Haematology 4005:10.1002/14651858.CD011960.pub2 3580:British Journal of Haematology 3384:American Journal of Hematology 1690:Indicators of a poor prognosis 1680:Indicators of a good prognosis 1405:Myelodysplasia unclassifiable 465:and abnormal chromosome number 358:. Some people can be cured by 334:. Supportive care may include 275:Risk factors include previous 268:. Some types may develop into 1: 5107:Chronic eosinophilic leukemia 4866:Chronic neutrophilic leukemia 2592:Rasel M, Mahboobi SK (2022), 2405:10.1182/hematology.2020000163 1476:New categories in WHO 5th ed. 1231:chronic eosinophilic leukemia 596:MDS is thought to arise from 5447:Biphenotypic acute leukaemia 5382:Xanthelasmoidal mastocytosis 3922:(Press release). 7 July 2020 3918:Food and Drug Administration 3835:Journal of Clinical Oncology 3807:10.1182/blood-2006-05-021162 3655:Journal of Clinical Oncology 3616:Journal of Clinical Oncology 3544:Journal of Clinical Oncology 3347:10.1182/blood-2007-05-092304 3131:10.1182/blood-2016-09-687889 2989:10.3109/10428194.2012.742528 2783:10.1016/j.exphem.2013.04.008 2643:10.1182/blood-2014-10-551465 2502:10.3324/haematol.2010.025619 2448:Journal of Clinical Oncology 2226:Holland-Frei Cancer Medicine 2223:Hong WK, Holland JF (2010). 1890:chronic myelogenous leukemia 1536:Food and Drug Administration 1233:and is a sign of aberrancy. 1109:Hypogranular neutrophils or 146:, certain chemicals such as 4824:Acute myeloblastic leukemia 4510:The New York Times Magazine 3968:(1232): 31–32. April 2006. 3275:10.1016/j.ymgme.2012.07.011 3035:10.1016/j.bbcan.2014.05.004 2624:Wolach O, Stone RM (2015). 2594:"Transfusion Iron Overload" 2339:"Myelodysplastic Syndromes" 2077:"Myelodysplastic Syndromes" 2027:Myeloproliferative syndrome 1342:Refractory thrombocytopenia 1102:Hyposegmented neutrophils ( 886:, and other tissue-forming 46:Preleukemia, myelodysplasia 5493: 5344:Erythrodermic mastocytosis 5111:Hypereosinophilic syndrome 4423:Staff J (4 January 2009). 3486:10.1182/blood-2004-01-0338 2684:10.1182/blood-2002-07-2006 2563:10.1016/j.beha.2018.10.002 1567:(Inqovi) is a fixed-dosed 1545:: 21-month median survival 1333:with unilineage dysplasia 1131:with translocation t(8;21) 626:acute myelogenous leukemia 624:), then transformation to 471:acute myelogenous leukemia 463:chromosomal translocations 69:pseudo-Pelger-Huet nucleus 5477:Syndromes affecting blood 5159:Essential thrombocythemia 3556:10.1200/JCO.2000.18.5.956 3230:10.1007/s11899-016-0338-x 3181:10.1007/s12185-017-2285-2 2545:Bejar R (December 2018). 2189:10.3238/arztebl.2013.0783 1635:are available in the US, 1605:stem cell transplantation 1416:(dysplasia in childhood) 1321:Myelodysplastic syndrome 1310:World Health Organization 1282:Chanarin-Dorfman syndrome 1154:Erythroid nuclear budding 1148:erythroid precursors and 798:Splicing factor mutations 687:) of three (the third is 319:), in the bone marrow or 191:stem cell transplantation 71:is shown. There are also 59: 50: 18:Myelodysplastic syndromes 4771:hematological malignancy 4552:Myelodysplastic syndrome 4547:templates for discussion 4476:"Remembering Carl Sagan" 4200:10.1182/blood.V89.6.2079 3848:10.1200/JCO.2006.09.4169 3668:10.1200/JCO.2005.05.4346 2460:10.1200/JCO.2010.31.3080 1639:for intravenous use and 823:isocitrate dehydrogenase 587:acquired aplastic anemia 230:myelodysplastic syndrome 38:Myelodysplastic syndrome 4928:Philadelphia chromosome 3628:10.1200/JCO.2002.04.117 1592:all-trans retinoic acid 1565:Decitabine/cedazuridine 1172:is a sign of aberrancy. 1062:disorder in the marrow. 1050:balanced translocations 1007:Bone marrow examination 739:Hematopoietic stem cell 705:hematopoietic stem cell 326:Treatments may include 236:) is one of a group of 2854:Clinics in Haematology 2831:10.1038/sj.leu.2405055 1873:acute myeloid leukemia 1583:hypomethylating agents 1581:Chemotherapy with the 1569:combination medication 1518:bone marrow transplant 1338:Refractory neutropenia 1260:Differential diagnosis 1111:pseudo Chediak-Higashi 851:inactivating mutations 459:Chromosome abnormality 383: 352:antithymocyte globulin 270:acute myeloid leukemia 207:antithymocyte globulin 5442:Primary myelofibrosis 5374:Systemic mastocytosis 5319:Systemic mastocytosis 4575:10.1093/annonc/mdu180 4569:(Suppl 3): iii57–69. 4429:Winston-Salem Journal 1631:.Currently, two iron 1288:, and other poisons. 1088:Granulocytic series: 997:monoclonal gammopathy 876:embryonic development 751:repairing damaged DNA 695:to treat MDS. Proper 593:can evolve into MDS. 381: 5364:Solitary mastocytoma 5354:Urticaria pigmentosa 5260:Sideroblastic anemia 3889:10.1056/NEJMoa061292 2949:10.1056/NEJMoa041668 2733:10.3390/ijms16010966 2022:Clonal hematopoiesis 1702:prognostic factors: 1188:Perls' Prussian blue 1115:azurophilic granules 1021:bone marrow aspirate 872:transcription factor 853:, in one of the two 763:base excision repair 539:sideroblastic anemia 330:, drug therapy, and 4482:. 9 November 2012. 3079:10.1038/leu.2015.91 2893:1974Natur.251..437V 1929:President of Panama 1336:Refractory anemia, 1184:Ringed sideroblasts 1099:/folate deficiency) 1095:(also seen in vit B 1060:lymphoproliferative 1042:Virtual karyotyping 937:and examination of 671:The recognition of 254:shortness of breath 111:shortness of breath 5309:Mast cell leukemia 5201:Erythroleukemia/M6 5085:Acute eosinophilic 4696:External resources 4246:10.1007/BF02994001 3758:10.1002/cncr.21792 3709:10.1002/cncr.22376 2314:"Thrombocytopenia" 2255:"Anemia: Overview" 1925:Laurentino Cortizo 1454:MDS unclassifiable 1448:myeloproliferative 1142:Erythroid series: 1104:pseudo Pelger-Huet 999:: Age-appropriate 864:autosomal dominant 755:chromosomal breaks 728:ringed sideroblast 573:such as busulfan, 384: 374:Signs and symptoms 336:blood transfusions 258:bleeding disorders 240:in which immature 177:bone marrow biopsy 5472:Myeloid neoplasia 5459: 5458: 5455: 5454: 5390: 5389: 5359:Mast cell sarcoma 5314:Mast cell sarcoma 5282: 5281: 5278: 5277: 5245:Refractory anemia 5223:Polycythemia vera 5174: 5173: 5123: 5122: 5119: 5118: 5058: 5057: 5023: 5022: 5003: 5002: 4941: 4940: 4874: 4873: 4733: 4732: 4512:. 4 December 2005 4456:on April 14, 2016 4449:Los Angeles Times 4379:. 14 January 2007 4123:978-0-07-139140-5 3397:10.1002/ajh.20864 2236:978-1-60795-014-1 2145:on 5 October 2016 1965:, baseball player 1903: 1902: 1813:Refractory anemia 1718:virtual karyotype 1656:chelation therapy 1423: 1422: 1254:erythroid islands 1175:PAS (globular in 1075:dyserythropoiesis 1067:copper deficiency 1011:hematopathologist 874:critical for the 804:ring sideroblasts 657:blood transfusion 571:alkylating agents 397:count or reduced 281:radiation therapy 226: 225: 171:Diagnostic method 144:radiation therapy 32:Medical condition 16:(Redirected from 5484: 5435: 5408: 5399: 5395:Multiple/unknown 5375: 5332: 5302: 5293: 5238: 5216: 5194: 5185: 5152: 5143: 5134: 5100: 5078: 5069: 5050:Acute basophilic 5043: 5034: 4983: 4961: 4952: 4921: 4894: 4885: 4859: 4817: 4808: 4799: 4790: 4760: 4753: 4746: 4737: 4601: 4596: 4586: 4522: 4521: 4519: 4517: 4502: 4496: 4495: 4493: 4491: 4472: 4466: 4465: 4463: 4461: 4452:. Archived from 4439: 4433: 4432: 4420: 4414: 4413: 4411: 4410: 4395: 4389: 4388: 4386: 4384: 4369: 4363: 4362: 4351: 4345: 4344: 4307: 4301: 4300: 4272: 4266: 4265: 4229: 4223: 4219: 4213: 4212: 4202: 4178: 4172: 4171: 4134: 4128: 4127: 4111: 4101: 4095: 4094:"PMID 34887690" 4092: 4086: 4082: 4076: 4075: 4057: 4033: 4027: 4026: 4016: 3984: 3978: 3977: 3957: 3951: 3948: 3942: 3936: 3935: 3931: 3929: 3927: 3908: 3902: 3901: 3891: 3867: 3861: 3860: 3850: 3826: 3820: 3819: 3809: 3785: 3779: 3778: 3760: 3736: 3730: 3729: 3711: 3687: 3681: 3680: 3670: 3661:(24): 3895–903. 3646: 3640: 3639: 3610: 3604: 3603: 3574: 3568: 3567: 3538: 3532: 3531: 3529: 3528: 3513: 3507: 3506: 3488: 3464: 3458: 3454: 3448: 3444: 3438: 3434: 3428: 3424: 3418: 3417: 3399: 3375: 3369: 3368: 3358: 3326: 3320: 3319: 3317: 3316: 3302: 3296: 3293: 3287: 3286: 3258: 3252: 3251: 3241: 3209: 3203: 3200: 3194: 3193: 3183: 3159: 3153: 3152: 3142: 3110: 3101: 3100: 3090: 3058: 3047: 3046: 3017: 3011: 3010: 3000: 2968: 2962: 2961: 2951: 2927: 2921: 2920: 2901:10.1038/251437a0 2887:(5474): 437–38. 2876: 2870: 2869: 2849: 2843: 2842: 2814: 2805: 2804: 2794: 2762: 2756: 2755: 2745: 2735: 2711: 2705: 2704: 2686: 2677:(5): 1996–2000. 2662: 2656: 2655: 2645: 2621: 2615: 2614: 2613: 2612: 2589: 2583: 2582: 2542: 2536: 2533: 2524: 2523: 2513: 2481: 2472: 2471: 2442: 2436: 2433: 2427: 2426: 2416: 2384: 2378: 2375: 2354: 2353: 2351: 2349: 2335: 2329: 2328: 2326: 2324: 2310: 2304: 2301: 2295: 2294: 2292: 2290: 2276: 2270: 2269: 2267: 2265: 2251: 2245: 2244: 2220: 2211: 2210: 2200: 2168: 2155: 2154: 2152: 2150: 2135: 2092: 2091: 2089: 2087: 2073: 2067: 2066: 2064: 2062: 2047:"Myelodysplasia" 2043: 1988:, astrophysicist 1907:Cleveland Clinic 1791: 1630: 1318: 1286:arsenic toxicity 1205:Hypersegmented ( 1123:– automatically 1001:cancer screening 993:hemolytic anemia 947:thrombocytopenia 943:hemolytic anemia 935:Full blood count 909:of noncancerous 845:GATA2 deficiency 726:deposits in the 547:GATA2 deficiency 526:Vietnam veterans 502:cyclophosphamide 414:Thrombocytopenia 313:white blood cell 55: 35: 21: 5492: 5491: 5487: 5486: 5485: 5483: 5482: 5481: 5462: 5461: 5460: 5451: 5429: 5424: 5420:Myeloid sarcoma 5402: 5386: 5373: 5368: 5328: 5323: 5296: 5274: 5232: 5227: 5210: 5205: 5188: 5170: 5146: 5115: 5094: 5089: 5072: 5054: 5037: 5019: 4999: 4977: 4972: 4955: 4937: 4915: 4910: 4888: 4870: 4853: 4848: 4811: 4782: 4773: 4764: 4734: 4729: 4728: 4691: 4690: 4612: 4560: 4550: 4531: 4526: 4525: 4515: 4513: 4504: 4503: 4499: 4489: 4487: 4474: 4473: 4469: 4459: 4457: 4441: 4440: 4436: 4422: 4421: 4417: 4408: 4406: 4397: 4396: 4392: 4382: 4380: 4371: 4370: 4366: 4353: 4352: 4348: 4309: 4308: 4304: 4283:(11): 1018–28. 4274: 4273: 4269: 4231: 4230: 4226: 4220: 4216: 4180: 4179: 4175: 4136: 4135: 4131: 4124: 4103: 4102: 4098: 4093: 4089: 4083: 4079: 4035: 4034: 4030: 3999:(8): CD011960. 3986: 3985: 3981: 3959: 3958: 3954: 3949: 3945: 3933: 3925: 3923: 3910: 3909: 3905: 3882:(14): 1456–65. 3869: 3868: 3864: 3841:(25): 3884–91. 3828: 3827: 3823: 3787: 3786: 3782: 3751:(8): 1794–803. 3738: 3737: 3733: 3689: 3688: 3684: 3648: 3647: 3643: 3622:(10): 2429–40. 3612: 3611: 3607: 3576: 3575: 3571: 3540: 3539: 3535: 3526: 3524: 3515: 3514: 3510: 3466: 3465: 3461: 3455: 3451: 3445: 3441: 3435: 3431: 3425: 3421: 3377: 3376: 3372: 3328: 3327: 3323: 3314: 3312: 3304: 3303: 3299: 3294: 3290: 3260: 3259: 3255: 3211: 3210: 3206: 3201: 3197: 3161: 3160: 3156: 3125:(15): 2103–10. 3112: 3111: 3104: 3073:(11): 2134–42. 3060: 3059: 3050: 3019: 3018: 3014: 2970: 2969: 2965: 2929: 2928: 2924: 2878: 2877: 2873: 2851: 2850: 2846: 2816: 2815: 2808: 2764: 2763: 2759: 2713: 2712: 2708: 2664: 2663: 2659: 2636:(16): 2477–85. 2623: 2622: 2618: 2610: 2608: 2591: 2590: 2586: 2544: 2543: 2539: 2534: 2527: 2483: 2482: 2475: 2444: 2443: 2439: 2434: 2430: 2386: 2385: 2381: 2376: 2357: 2347: 2345: 2337: 2336: 2332: 2322: 2320: 2312: 2311: 2307: 2302: 2298: 2288: 2286: 2278: 2277: 2273: 2263: 2261: 2253: 2252: 2248: 2237: 2222: 2221: 2214: 2170: 2169: 2158: 2148: 2146: 2137: 2136: 2095: 2085: 2083: 2075: 2074: 2070: 2060: 2058: 2045: 2044: 2040: 2035: 2012: 1919:Michael Brecker 1915: 1913:People with MDS 1782: 1768: 1756: 1739: 1737:Genetic markers 1673: 1651:Clinical trials 1628: 1613: 1507: 1501:/9L syndromes. 1497:deficiency and 1478: 1456: 1436: 1428: 1306: 1301: 1278:Jordans anomaly 1262: 1244:or surrounding 1180:classification) 1098: 1091:Hypersegmented 1036:genetic testing 969: 924: 911:megakaryoblasts 900: 847: 819: 800: 771: 736: 697:DNA methylation 669: 606:Differentiation 559: 557:Pathophysiology 494: 486:medical history 376: 328:supportive care 189:, medications, 187:Supportive care 33: 28: 23: 22: 15: 12: 11: 5: 5490: 5488: 5480: 5479: 5474: 5464: 5463: 5457: 5456: 5453: 5452: 5450: 5449: 5444: 5438: 5436: 5426: 5425: 5423: 5422: 5417: 5411: 5409: 5396: 5392: 5391: 5388: 5387: 5385: 5384: 5378: 5376: 5370: 5369: 5367: 5366: 5361: 5356: 5351: 5346: 5341: 5335: 5333: 5325: 5324: 5322: 5321: 5316: 5311: 5305: 5303: 5290: 5284: 5283: 5280: 5279: 5276: 5275: 5273: 5272: 5267: 5262: 5257: 5252: 5247: 5241: 5239: 5229: 5228: 5226: 5225: 5219: 5217: 5207: 5206: 5204: 5203: 5197: 5195: 5182: 5176: 5175: 5172: 5171: 5169: 5168: 5162: 5161: 5155: 5153: 5140: 5131: 5125: 5124: 5121: 5120: 5117: 5116: 5114: 5113: 5103: 5101: 5091: 5090: 5088: 5087: 5081: 5079: 5066: 5060: 5059: 5056: 5055: 5053: 5052: 5046: 5044: 5031: 5025: 5024: 5021: 5020: 5018: 5017: 5011: 5009: 5005: 5004: 5001: 5000: 4998: 4997: 4992: 4986: 4984: 4974: 4973: 4971: 4970: 4964: 4962: 4949: 4943: 4942: 4939: 4938: 4936: 4935: 4930: 4924: 4922: 4912: 4911: 4909: 4908: 4903: 4897: 4895: 4882: 4876: 4875: 4872: 4871: 4869: 4868: 4862: 4860: 4850: 4849: 4847: 4846: 4841: 4836: 4831: 4826: 4820: 4818: 4805: 4796: 4787: 4775: 4774: 4765: 4763: 4762: 4755: 4748: 4740: 4731: 4730: 4727: 4726: 4715: 4700: 4699: 4697: 4693: 4692: 4689: 4688: 4677: 4666: 4655: 4644: 4629: 4613: 4608: 4607: 4605: 4604:Classification 4598: 4597: 4558: 4534: 4530: 4529:External links 4527: 4524: 4523: 4497: 4480:Universe Today 4467: 4434: 4415: 4390: 4364: 4346: 4302: 4267: 4224: 4214: 4193:(6): 2079–88. 4173: 4129: 4122: 4096: 4087: 4077: 4028: 3979: 3952: 3943: 3903: 3862: 3821: 3780: 3731: 3682: 3641: 3605: 3569: 3533: 3508: 3459: 3449: 3439: 3429: 3419: 3370: 3341:(3): 1534–42. 3321: 3310:www.google.com 3297: 3288: 3269:(1–2): 25–30. 3253: 3204: 3195: 3154: 3102: 3048: 3012: 2963: 2922: 2871: 2860:(4): 1023–35. 2844: 2806: 2757: 2706: 2657: 2616: 2584: 2537: 2525: 2496:(8): 1236–40. 2473: 2437: 2428: 2379: 2355: 2330: 2305: 2296: 2271: 2246: 2235: 2212: 2183:(46): 783–90. 2156: 2093: 2068: 2037: 2036: 2034: 2031: 2030: 2029: 2024: 2019: 2011: 2008: 2007: 2006: 2000: 1995: 1989: 1983: 1977: 1975:James W. Nance 1972: 1966: 1960: 1954: 1948: 1942: 1937: 1931: 1922: 1914: 1911: 1901: 1900: 1893: 1883: 1877: 1876: 1869: 1863: 1857: 1856: 1853: 1847: 1841: 1840: 1836: 1830: 1824: 1823: 1816: 1810: 1804: 1803: 1800: 1797: 1781: 1778: 1767: 1764: 1755: 1752: 1738: 1735: 1714: 1713: 1710: 1707: 1672: 1669: 1665:kidney failure 1629:< 1000 µg/L 1624:serum ferritin 1612: 1609: 1579: 1578: 1572: 1562: 1556: 1546: 1522:erythropoietin 1506: 1503: 1477: 1474: 1473: 1472: 1469: 1466: 1463: 1455: 1452: 1444:thrombocytosis 1435: 1432: 1427: 1424: 1421: 1420: 1417: 1410: 1409: 1406: 1402: 1401: 1398: 1392: 1391: 1385: 1378: 1377: 1374: 1367: 1366: 1353: 1346: 1345: 1334: 1326: 1325: 1322: 1305: 1302: 1300: 1299:Classification 1297: 1261: 1258: 1223: 1222: 1221: 1220: 1213: 1211:megakaryocytes 1203: 1197: 1196: 1195: 1181: 1173: 1162: 1155: 1152: 1140: 1139: 1138: 1132: 1118: 1107: 1100: 1096: 1071: 1070: 1063: 1056:Flow cytometry 1053: 1039: 1028: 1014: 1004: 981:kidney failure 979:deficiencies, 967: 954: 923: 920: 899: 896: 846: 843: 818: 808: 799: 796: 770: 767: 735: 732: 712:acute leukemia 668: 665: 591:Fanconi anemia 558: 555: 543:Fanconi anemia 493: 490: 467: 466: 456: 453: 444: 437: 436: 411: 402: 375: 372: 305:red blood cell 264:, or frequent 224: 223: 220: 214: 213: 200: 194: 193: 184: 180: 179: 173: 167: 166: 158:, exposure to 136: 130: 129: 128:~ 70 years old 126: 122: 121: 103: 97: 96: 87: 81: 80: 57: 56: 48: 47: 44: 40: 39: 31: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 5489: 5478: 5475: 5473: 5470: 5469: 5467: 5448: 5445: 5443: 5440: 5439: 5437: 5434: 5433: 5427: 5421: 5418: 5416: 5413: 5412: 5410: 5407: 5406: 5400: 5397: 5393: 5383: 5380: 5379: 5377: 5371: 5365: 5362: 5360: 5357: 5355: 5352: 5350: 5347: 5345: 5342: 5340: 5337: 5336: 5334: 5331: 5326: 5320: 5317: 5315: 5312: 5310: 5307: 5306: 5304: 5301: 5300: 5294: 5291: 5289: 5285: 5271: 5268: 5266: 5263: 5261: 5258: 5256: 5253: 5251: 5248: 5246: 5243: 5242: 5240: 5237: 5236: 5230: 5224: 5221: 5220: 5218: 5215: 5214: 5208: 5202: 5199: 5198: 5196: 5193: 5192: 5186: 5183: 5181: 5177: 5167: 5164: 5163: 5160: 5157: 5156: 5154: 5151: 5150: 5144: 5141: 5139: 5135: 5132: 5130: 5126: 5112: 5108: 5105: 5104: 5102: 5099: 5098: 5092: 5086: 5083: 5082: 5080: 5077: 5076: 5070: 5067: 5065: 5061: 5051: 5048: 5047: 5045: 5042: 5041: 5035: 5032: 5030: 5026: 5016: 5015:Histiocytosis 5013: 5012: 5010: 5006: 4996: 4993: 4991: 4988: 4987: 4985: 4982: 4981: 4975: 4969: 4966: 4965: 4963: 4960: 4959: 4953: 4950: 4948: 4947:Myelomonocyte 4944: 4934: 4931: 4929: 4926: 4925: 4923: 4920: 4919: 4913: 4907: 4904: 4902: 4899: 4898: 4896: 4893: 4892: 4886: 4883: 4881: 4877: 4867: 4864: 4863: 4861: 4858: 4857: 4851: 4845: 4842: 4840: 4837: 4835: 4832: 4830: 4827: 4825: 4822: 4821: 4819: 4816: 4815: 4809: 4806: 4804: 4800: 4797: 4795: 4791: 4788: 4786: 4780: 4776: 4772: 4768: 4761: 4756: 4754: 4749: 4747: 4742: 4741: 4738: 4725: 4721: 4720: 4716: 4714: 4711: 4707: 4706: 4702: 4701: 4698: 4694: 4687: 4683: 4682: 4678: 4676: 4672: 4671: 4667: 4665: 4661: 4660: 4656: 4654: 4650: 4649: 4645: 4643: 4639: 4638: 4634: 4630: 4628: 4624: 4623: 4619: 4615: 4614: 4611: 4606: 4602: 4594: 4590: 4585: 4580: 4576: 4572: 4568: 4564: 4559: 4557: 4553: 4548: 4544: 4543: 4538: 4533: 4532: 4528: 4511: 4507: 4501: 4498: 4485: 4481: 4477: 4471: 4468: 4455: 4451: 4450: 4445: 4438: 4435: 4430: 4426: 4419: 4416: 4404: 4400: 4394: 4391: 4378: 4374: 4368: 4365: 4360: 4356: 4350: 4347: 4342: 4338: 4334: 4330: 4326: 4322: 4319:(4): 451–58. 4318: 4314: 4306: 4303: 4298: 4294: 4290: 4286: 4282: 4278: 4271: 4268: 4263: 4259: 4255: 4251: 4247: 4243: 4240:(4): 405–10. 4239: 4235: 4228: 4225: 4218: 4215: 4210: 4206: 4201: 4196: 4192: 4188: 4184: 4177: 4174: 4169: 4165: 4161: 4157: 4153: 4149: 4146:(2): 346–56. 4145: 4141: 4133: 4130: 4125: 4119: 4115: 4110: 4109: 4100: 4097: 4091: 4088: 4081: 4078: 4073: 4069: 4065: 4061: 4056: 4051: 4047: 4043: 4039: 4032: 4029: 4024: 4020: 4015: 4010: 4006: 4002: 3998: 3994: 3990: 3983: 3980: 3975: 3971: 3967: 3963: 3956: 3953: 3947: 3944: 3940: 3939:public domain 3921: 3919: 3913: 3907: 3904: 3899: 3895: 3890: 3885: 3881: 3877: 3873: 3866: 3863: 3858: 3854: 3849: 3844: 3840: 3836: 3832: 3825: 3822: 3817: 3813: 3808: 3803: 3799: 3795: 3791: 3784: 3781: 3776: 3772: 3768: 3764: 3759: 3754: 3750: 3746: 3742: 3735: 3732: 3727: 3723: 3719: 3715: 3710: 3705: 3702:(2): 265–73. 3701: 3697: 3693: 3686: 3683: 3678: 3674: 3669: 3664: 3660: 3656: 3652: 3645: 3642: 3637: 3633: 3629: 3625: 3621: 3617: 3609: 3606: 3601: 3597: 3593: 3589: 3586:(2): 349–57. 3585: 3581: 3573: 3570: 3565: 3561: 3557: 3553: 3550:(5): 956–62. 3549: 3545: 3537: 3534: 3522: 3518: 3512: 3509: 3504: 3500: 3496: 3492: 3487: 3482: 3479:(2): 579–85. 3478: 3474: 3470: 3463: 3460: 3453: 3450: 3443: 3440: 3433: 3430: 3423: 3420: 3415: 3411: 3407: 3403: 3398: 3393: 3390:(7): 625–30. 3389: 3385: 3381: 3374: 3371: 3366: 3362: 3357: 3352: 3348: 3344: 3340: 3336: 3332: 3325: 3322: 3311: 3307: 3301: 3298: 3292: 3289: 3284: 3280: 3276: 3272: 3268: 3264: 3257: 3254: 3249: 3245: 3240: 3235: 3231: 3227: 3224:(5): 333–41. 3223: 3219: 3215: 3208: 3205: 3199: 3196: 3191: 3187: 3182: 3177: 3174:(2): 175–82. 3173: 3169: 3165: 3158: 3155: 3150: 3146: 3141: 3136: 3132: 3128: 3124: 3120: 3116: 3109: 3107: 3103: 3098: 3094: 3089: 3084: 3080: 3076: 3072: 3068: 3064: 3057: 3055: 3053: 3049: 3044: 3040: 3036: 3032: 3029:(2): 326–41. 3028: 3024: 3016: 3013: 3008: 3004: 2999: 2994: 2990: 2986: 2983:(7): 1364–6. 2982: 2978: 2977:Leuk Lymphoma 2974: 2967: 2964: 2959: 2955: 2950: 2945: 2942:(6): 549–57. 2941: 2937: 2933: 2926: 2923: 2918: 2914: 2910: 2906: 2902: 2898: 2894: 2890: 2886: 2882: 2875: 2872: 2867: 2863: 2859: 2855: 2848: 2845: 2840: 2836: 2832: 2828: 2824: 2820: 2813: 2811: 2807: 2802: 2798: 2793: 2788: 2784: 2780: 2777:(8): 665–74. 2776: 2772: 2768: 2761: 2758: 2753: 2749: 2744: 2739: 2734: 2729: 2726:(1): 966–89. 2725: 2721: 2720:Int J Mol Sci 2717: 2710: 2707: 2702: 2698: 2694: 2690: 2685: 2680: 2676: 2672: 2668: 2661: 2658: 2653: 2649: 2644: 2639: 2635: 2631: 2627: 2620: 2617: 2607: 2603: 2599: 2595: 2588: 2585: 2580: 2576: 2572: 2568: 2564: 2560: 2556: 2552: 2548: 2541: 2538: 2532: 2530: 2526: 2521: 2517: 2512: 2507: 2503: 2499: 2495: 2491: 2490:Haematologica 2487: 2480: 2478: 2474: 2469: 2465: 2461: 2457: 2454:(4): 428–34. 2453: 2449: 2441: 2438: 2432: 2429: 2424: 2420: 2415: 2410: 2406: 2402: 2398: 2394: 2390: 2383: 2380: 2374: 2372: 2370: 2368: 2366: 2364: 2362: 2360: 2356: 2344: 2340: 2334: 2331: 2319: 2315: 2309: 2306: 2300: 2297: 2285: 2281: 2280:"Neutropenia" 2275: 2272: 2260: 2256: 2250: 2247: 2242: 2238: 2232: 2228: 2227: 2219: 2217: 2213: 2208: 2204: 2199: 2194: 2190: 2186: 2182: 2178: 2174: 2167: 2165: 2163: 2161: 2157: 2144: 2140: 2134: 2132: 2130: 2128: 2126: 2124: 2122: 2120: 2118: 2116: 2114: 2112: 2110: 2108: 2106: 2104: 2102: 2100: 2098: 2094: 2082: 2078: 2072: 2069: 2056: 2052: 2048: 2042: 2039: 2032: 2028: 2025: 2023: 2020: 2017: 2014: 2013: 2009: 2004: 2001: 1999: 1996: 1993: 1990: 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