1532:
LMP1/2-expressing cells. Nine patients had durable (>4 years) remissions, 1 patient had a complete remission which lasted only 9 months, and 2 patients show no response to the treatment. In a second study, 8 patients with localized and two with advanced disease who were in complete remission after chemotherapy (with or without radiation treatment) were given their own CTL that had been engineered to kill LMP1/2-bearing cells. One patient relapsed after 32 months while the remaining 7 patients had progression-free and overall survivals of 100 and 90%, respectively. A phase I clinical trial sponsored by Baylor
College of Medicine, the Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, and the Methodist Hospital System is recruiting individuals to test the effects of donor CTL engineered to kill cells bearing LMP1/2, ARF, and/or EBNA-1 viral antigens. A phase 2 clinical study sponsored by ViGenCell Inc. is being conducted at the Catholic University of Korea to test the effects of CTL engineered to kill EBV-infected cells on patients that are in complete remission following chemotherapy (±radiation treatment) but at high risk for recurrent disease. Patients will receive the CTL or
1293:
patients with limited (i.e. stage I or II) disease involving other sites in the head area are more likely to have a relatively slow progression of their disease while patients with stage III or IV disease have a more rapidly progressive disease with a poor prognosis. Patients presenting with ENKTCL-NT that does not involve the head area typically have a disseminated and aggressively progressive disease with a very poor prognosis. Patients with stage I or II localized disease that have been treated with the recently defined chemotherapeutic protocols have 5 year survivals of ~70–89% while those with advanced stage III or IV disseminated disease treated with these protocols have 5 year survivals of 50%. Patients who relapse or are resistant to these protocols have had overall survivals of just a few months.
50:
1297:
disease, no nasal involvement, distant lymph node involvement, and detectable blood levels of EBV DNA) to define patients as low, intermediate, and high risk based on their having 0–1, 2, or 3–5 risk factors, respectively. Overall 3 year survival in these 3 respective groups were 81, 55, and 28%. Patients, particularly those in the advanced poor risk groups may develop hemophagocytic lymphohistiocytosis or have their disease progress to aggressive NK-cell leukemia. Both conditions are life-threatening and far less responsive to treatment.
240:, uterus, testes, and/or elsewhere. Rarely, individuals present with evidence of involvement in the later sites without those involving the head/neck area. On further study these individuals may be found to have occult involvement in the head and neck or to develop such involvement. However, ~10 present of patients present with only skin lesions such as a solitary or multiple subcutaneous masses (which may be ulcerated) in the arms or legs while another ~10% present with masses in the lower
244:(which may be accompanied by bleeding or obstruction), salivary glands, testes, muscles, or other organs without evidence of lesions in the head/neck areas. In these cases, there is relatively little involvement of lymph nodes except as a result of direct invasion from non-nodal sites. Thirty-five to forty-five percent of patients present with a history of
279:. Quantification of these levels at diagnosis correlates with the extent of their tumor load while serially assaying these levels during treatment gives evidence of the tumors response to treatment and residual disease. Rarely, patients show laboratory evidence of hemophagocytic lymphohistiocytosis such as: decreased circulating
1601:(e.g. RK-33) are being study in pre-clinical in vitro experiments as potential inhibitors of malignant NK/T cell proliferation and survival. They are in further studies to test them as potential therapeutic agents in ENKTCL-NT patients that have activating mutations or overexpression of the cited targets.
138:, skin, and various other tissues. ENKTCL-NT mainly affects adults; it is relatively common in Asia and to lesser extents Mexico, Central America, and South America but is rare in Europe and North America. In Korea, ENKTCL-NT often involves the skin and is reported to be the most common form of cutaneous
1194:
product. Studies conducted on the expression of microRNAs in cultured malignant NK cells have also revealed that many are either over- or under-expressed compared to non-malignant cultured NK cells. This dysregulation of these microRNA genes may reflect the action of products expressed by certain EBV
215:
Extranodal NK/T-cell lymphoma, nasal type occurs primarily in Asians and South
Americans; it is comparatively uncommon in other areas. Affected patients (median age 50–60 years old; males predominate) most often (~80% of cases) present with nasal bleeding, upper airway obstruction, perforation of the
1431:
There are numerous regimens that use non-chemotherapeutic agents to target specific elements known or thought to be involved in the survival of the malignant cells in a significant percentage of ENKTCL-NT cases. The targets should be determined as overexpressed or present in the malignant tissues of
1262:
scans are recommended to determine the extent of disease at presentation as well as to follow the effects of therapeutic interventions. The tumor load of each individual's disease as well as response to therapies has also been estimated by assaying plasma levels of EBV DNA. ENKTCL-NT can be mimicked
912:
In the above table, ARID1A protein stands for AT-rich interactive domain-containing protein 1A and ECSIT protein stands for evolutionarily conserved signaling intermediate in Toll pathway; mitochondrial. A gain of function mutation in the ECSIT gene that changes the amino acid at the 140 position in
364:
ENKTCL-NT is thought to arise from the expression of EBV genes in the infected NK or cytotoxic T cells and the ability of these genes to cause the cells they infect to overexpress and acquire mutations in key genes that regulate cell growth, immortalization, invasiveness, and ability to evade normal
206:
regimens greatly improved survival in cases of early disease. While, survival in advanced cases is still extremely poor, generally being only a few months, recent studies suggest that new regimens directed at gene mutation and expression abnormalities may improve survival. Further study of these new
1467:
receptor on lymphocytes thereby blocking the action of PD-L1 in suppressing the anti-cancer actions of these cells. Seven patients with refractory or relapsed ENKTCL-NT had either complete (5 patients) or partial (2 patients) responses to
Pembrolizumab and three patients with relapsed ENKTCL-NT had
1275:
may also mimic ENKTCL-NT. This chronic disorder involves the proliferation of CD+4, CD8+, CD4-/CD8-, or CD4+/CD8+ T cells in the mucosal layers of the GI tract to give a variety of GI tract symptoms. While generally a persistent and benign disorder, a small but significant percentage of cases have
499:
Subsequent studies showed that the disease is also occasionally associated with losses in the short arm of chromosome 8 at position 11.23 (8p11.23) which for unclear reasons are associated with a poor prognosis, and occasional losses at position 11l.2 in the q arm of chromosome 14 (14q11.2) which
397:
phase of infectivity. EBV has three different latency phases, I, II, and III, in each of which different sets of latency genes are expressed to establish different controls on the cells which they infect. In the premalignant cells of ENKTCL-NT, EBV express latency II genes such as EBNA-1, LMP-1,
1531:
and therefore are potential targets for attack by cytotoxic T cells (CTL). Studies have used CTL that have been engineered to attack and kill LMP1 and/or LMP2 expressing cells. Eleven patients with refractory or relapsed ENKTCL-NT were treated with their own CTL that had been engineered to kill
1292:
The course of the untreated disease is heavily dependent on its clinical stage at diagnosis. Patients presenting with highly localized stage I nasal disease usually have nasal but no other symptoms; these individuals commonly show no progression of their disease over long periods of time. Other
1296:
Three prognostic models, NK-PI, PINK (i.e. prognostic index of natural killer lymphomas), and PINK-E) for ENKTCL-NT have evolved over the past 12 years. The latest model, PINK-E, which applies to patients treated with recently defined regimens, lists 5 risk factors (age >60, state III or IV
1237:
assays to detect one of the virus's latent products, typically EBER-1/2 micoRNAs. Identification of the genetic abnormalities cited above in the cells may be of help in establishing the diagnoses and be of use for selecting novel therapeutic approaches to individual patients. Non-malignant
181:, asymptomatic form, and for unclear reasons becomes active in causing the disease. Following the virus's activation, the infected cells acquire numerous genetic abnormalities which may play an important role in the development and/or progression of ENKTCL-NT.
426:
proteins which when overexpressed block these cells' apoptosis (i.e. cell death) response to injury or the host's immune system and promote their survival and proliferation; LMP2A and LMP2B proteins induce infected cells to overexpress the genes that make
264:. Also in rare cases, patients evidence a widespread disease that includes malignant cell infiltrations in the liver, spleen, lymph nodes, bone marrow, and/or blood. These case are, or may soon progress to, a related but potentially fatal disease,
1092:
In consequence of, or addition to the cited genetic abnormalities, ENKTCL-NT malignant cells have overly active the; JAK-STAT signaling pathway that in the cancer setting promotes cell proliferation, survival, and other pro-malignant behaviors;
435:
proteins and to activate the NF-κ pathway which when over-activated blocks these cells' apoptosis response and promotes their survival and proliferation; EBER 1 and 2 non-coding RNAs induce infected cells to overexpress the gene that makes the
2914:
Sharma A, Oishi N, Boddicker RL, Hu G, Benson HK, Ketterling RP, Greipp PT, Knutson DL, Kloft-Nelson SM, He R, Eckloff BW, Jen J, Nair AA, Davila JI, Dasari S, Lazaridis KN, Bennani NN, Wu TT, Nowakowski GS, Murray JA, Feldman AL (May 2018).
3190:
1516:
is almost always expressed in the malignant cells of ENkTCL-NT. One patient with this disease, after relapsing following each of two chemotherapy courses, had a complete remission when treated with a cytotoxic antibody directed at CD38,
260:. Most (70–75%) patients are diagnosed with early stage I or II disease while the rest have far more serious stage III or IV disease. Rarely, patients with stage III or IV disease have evidence of a life-threatening complication,
457:
The rapidly proliferating and immortalized EBV-infected NK/T cells accumulate numerous changes in the expression or activity of their genes by acquisition of chromosome deletions, gene mutations, and changes in gene expression.
1272:
440:
protein which when overexpressed may promote its parent cells to proliferate and avoid the host's immune system; and certain BART microRNAs may help infected cells avoid attack by the hosts immune system and modify their
4146:
315:(e.g. decreased circulating red blood cells, leukocytes, and/or platelets, increased circulating large, granule-containing malignant NK cells, and infiltrations of the latter cells in bone marrow and other tissues).
1625:
1361:(e.g.carboplatin) were active on theses cells. Accordingly, several chemotherapeutic regimens were tested and found to give much better results than previous regimens. However, these regimens have bot undergone
150:
369:. Since these gene-related abnormalities are multiple and vary between patients, it is not clear which contribute to the development and/or progression of ENKTCL-NT. Clinical studies are therefore examining
1101:
that in the cancer setting promotes cellular differentiation and proliferation; and NF-κB signaling that in the cancer setting promotes cell survival and proliferation. Studies suggest that that overactive
3890:
1506:, was helpful in treating relapsed ENKTCL-NT. A not-yet-recruiting study estimated to be finished by Sept., 2018 examines the effects of brentuxixmab vedotin on EBV-positive, CD30-positive lymphomas.
3131:"Administration of Most Closely Matched Third Party Rapidly Generated LMP, BARF1 and EBNA1 Specific CytotoxicT-Lymphocytes to Patients With EBV-Positive Lymphoma and Other EBV-Positive Malignancies"
57:
Histopathology of extranodal NK-T cell lymphoma, nasal type (H&E stain). These lymphoma cells are typically monotonous, with folded nuclei, indistinct nucleoli and moderate amount of cytoplasm.
1472:
in New York City is recruiting individuals to study the effects of
Pembrolizumab in patients with early-stage ENKTCL-NT; a phase I/II clinical study sponsored by the Abramson Cancer Center of the
445:
thereby promoting their proliferation. In consequence, the EBV latency II genes force infected cells to become immortal, proliferate excessively, invade tissues, and avoid attack by the hosts'
1254:
The diagnosis of ENKTCL-NT depends on histological findings that biopsied tissue infiltrates contain lymphocytes that express CD3ε, cytotoxic molecules (granzyme B, perforin, TIA1), and EBV.
187:(EBV+ nodal NKTCL) was considered to be one form of ENKTCL-NT since it is a malignancy of EBV-infected NK or T cells. However, EBV+ nodal NKTCL is manifested primarily by its involvement in
3444:
3074:"Phase I/II Study of Pembrolizumab in Patients with Relapsed or Refractory Extranodal NK/T- Cell Lymphoma (ENKTL), Nasal Type and EBV-associated Diffuse Large B Cell Lymphomas (EBV-DLBCL)"
4225:
1211:
and cellular infiltrates that are centered around and often injure or destroy small blood vessels. The infiltrates contain large granule-containing lymphocytes that express cell surface
1521:. A phase 2 clinical study on the effects of Daratumumab on ENTCL-NT sponsored by Janssen Research & Development, LLC is recruiting patients in China, South Korea, and Taiwan.
389:
particles. In the premalignant precursor NK and cytotoxic T cells of ENKTCL-NT, these episomes express only some of their many latency genes, i.e. genes which promote the virus's
3561:
3205:
4151:
3960:
3116:"An Open Label, Phase 2 Study to Assess the Clinical Efficacy and Safety of Daratumumab in Patients with Relapsed or Refractory Natural Killer/T-Cell Lymphoma, Nasal Type"
196:
1409:, ifosfamide, L-asparaginase, and etoposide. The regimen obtains complete response and 5 year overall survival rates of 45 and 47%, respectively. In the United States,
4174:
1734:
1695:
1199:
gene. In all cases, the epigenetic dysregulation of these genes requires further study to determine its significance for the development and progression of ENKTCL-NT.
1480:
is recruiting individuals to examine the effects of
Pembrolizumab in individuals with relapsed or refractory ENKTCL-NA; and a clinical phase 2 study sponsored by the
3526:
1397:
plus radiation followed by etopoxide, ifosfamide, cisplatin, and dexamethasone to give complete response and 5 overall survival rates of 87 and 73%, respectively.
1393:). Five-year progression-free and overall survival rates with this regimen are 70–72% and 61–63%, respectively. An alternative regimen, termed CCRT-VIDL, combines
4215:
3916:
356:
precursors to most lymphomas in lymphatic tissues versus the frequent occupancy of the NK and cytotoxic T cells precursors to ENTCL-NT in non-lymphatic tissues.
3255:
1216:
1536:(i.e. peripheral blood mononuclear cells). The study, which begins recruitment in late Feb., 2019, seeks to determine if the CTL treatment prolongs remissions.
3606:
4119:
449:. Due at least in part to these imposed factors, the infected cells may acquire other genetic abnormalities that further promote their malignant behavior.
177:(EBV). Typically, the viral infection, which affects >90% of the world population, occurs years before evidence of ENKTCL-NT, is carried in cells in a
4158:
3704:
3449:
3583:
523:
have uncovered numerous genes which are mutated in the malignant cells of ENKTCL-NT. These mutated genes and their product proteins have the following
1337:) or chop-like regimens. These were only marginally successful because, as it was later discovered, the malignant NK cells in ENKTCL-NT over-express
3684:
3482:
3145:"A Phase 2 Study to Evaluate the Efficacy and Safety of Postremission Therapy Using VT-EBV-N in EBV Positive Extranodal NK/T Cell Lymphoma Patients"
1000:
4108:
3782:
3336:
236:. Less often, patients present with these findings plus signs and symptoms involving extranasal sites such as the skin, upper respiratory tract,
3955:
1469:
1128:, i.e. make less or none of their protein products. This silencing has been detected in numerous proteins expressed by cultured NK cells (e.g.
586:
373:
tactics to determine which gene abnormalities contribute to, and which drugs targeting these abnormalities are useful in treating, ENKTCL-NT.
3774:
3325:
1953:
1774:
Li DM, Lun LD (December 2012). "Mucor irregularis infection and lethal midline granuloma: a case report and review of published literature".
1758:
1370:
1366:
4103:
1417:
1701:- "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
3087:
3073:
3059:
202:
While a rare disease, particularly in North
America, ENKTCL-NT has recently gained much interest. Clinical studies have found that newer
4059:
3679:
3477:
3361:
1646:"Extranodal NK/T-Cell Lymphoma, Nasal Type: Genetic, Biologic, and Clinical Aspects with a Central Focus on Epstein-Barr Virus Relation"
49:
3144:
3130:
1271:, a disease wherein these cells infiltrative lesions are limited to the stomach. Another lymphoproliferative disorder of the GI tract,
3950:
1558:
925:
and thereby a relatively high mortality rate. Numerous other genes are rarely (i.e. ≤2% of cases) mutated in ENKTCL-NT. These include
922:
261:
191:; it also has clinical, pathological, pathophysiological, and genetic features that differ significantly from those of ENKTCL-NT. The
3015:
He SM, Li R, Kanwar JR, Zhou SF (2011). "Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1)".
500:
correlates with the ENKTCL-NT malignancy being of cytotoxic T cell origin. EBV-infected NK and T cells may also occasionally develop
3248:
2442:"Multivariate analysis of prognosis for patients with natural killer/T cell lymphoma-associated hemophagocytic lymphohistiocytosis"
3911:
1820:
Yamaguchi M, Oguchi M, Suzuki R (September 2018). "Extranodal NK/T-cell lymphoma: Updates in biology and management strategies".
275:; elevation in this serum enzyme is a poor prognostic indicator. Patients with ENKTCL-NT also have elevated levels of plasma EBV
3101:
348:), ENKTCL-NT commonly develops in non-lymphatic tissues. This difference in distribution probably reflects the occupancy of the
3159:"A Phase 2 Study of Venetoclax and Romidepsin with Safety Lead-In for Treatment of Relapsed/Refractory Mature T-Cell Lymphomas"
2669:
Peery RC, Liu JY, Zhang JT (October 2017). "Targeting survivin for therapeutic discovery: past, present, and future promises".
1268:
1264:
989:
4141:
4133:
3992:
3870:
3809:
3795:
3689:
3630:
3467:
3393:
1094:
1365:
that examine their effectiveness relative to other regimens. The following regimens are recommended by many studies and the
4189:
4099:
4049:
3945:
3674:
3458:
1358:
1220:
724:
4081:
3987:
3970:
3778:
3332:
3241:
1620:
1615:
1562:
225:
921:(i.e. V140A) is associated with a high incidence of ENKTCL-NT being complicated by the development of life-threatening
4022:
3895:
3601:
1566:
1178:
312:
265:
3158:
195:, 2016, therefore reclassified this lymphoma as a variant of a disease to which its features more closely resemble,
3937:
1976:
Rezk SA, Zhao X, Weiss LM (June 2018). "Epstein – Barr virus – associated lymphoid proliferations, a 2018 update".
1863:
Park S, Ko YH (January 2014). "Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorders".
1554:
1473:
828:
654:
1468:
had either complete (2 patients) or partial (1 patient) responses to
Nivolumab. A clinical study sponsored by the
1084:(PD-L1), that when up-regulated increases the ability of these cells to avoid attack by the host's immune system.
3825:
3666:
3588:
3102:"A Phase II Study of Brentuximab Vedotin in Patients with Relapsed or Refractory EBV-and CD30-positive Lymphomas"
1610:
1570:
1263:
by two benign diseases which involve the excessive proliferation of non-malignant NK cells in the GI tract viz.,
1081:
1067:
763:
473:'s was an early finding in occasional cases of ENKTCL-NT. This deletion removes one of the two copies of several
192:
4027:
3855:
3216:
1400:
Patients who have a partial response or relapse on this regimen are treated with the SMILE regimen (see below).
1267:, a disease wherein NK cell infiltrative lesions occur in the intestine, colon, stomach, and/or esophagus, and
773:
154:
114:
3493:
3115:
2826:"NK-Cell Enteropathy and Similar Indolent Lymphoproliferative Disorders: A Case Series With Literature Review"
1231:, and T cell intracellular antigen-1 (TIA-1). These cells exhibit evidence of EBV infection as determined by
512:
and thereby exhibit chaotic losses or increases in the expression of the genes located on these chromosomes.
2917:"Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract"
1499:
1481:
1464:
1255:
1098:
442:
42:
Angiocentric lymphoma, Nasal-type NK lymphoma, NK/T-cell lymphoma, Polymorphic/malignant midline reticulosis
4044:
3595:
2206:"The diagnosis and management of extranodal NK/T-cell lymphoma, nasal-type and aggressive NK-cell leukemia"
411:
403:
174:
81:
3921:
3900:
3814:
2867:"Indolent T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: a review and update"
1046:, a surface membrane protein that when up-regulated causes these cells to greatly increases the export of
1020:
1004:
501:
241:
237:
135:
1494:. Two case reports have indicated that the CD30-targeted monoclonal antibody, which is conjugated to the
4053:
3643:
3537:
1689:
1233:
1036:
272:
3616:
3439:
1377:
Localized stage I and 2 diseases are treated with a combination of local radiation followed by DeVIC (
207:
regimens has important implications not only for ENKTCL-NT but also for other NK/T cell malignancies.
3850:
3462:
3373:
2152:"The Genomics and Molecular Biology of Natural Killer/T-Cell Lymphoma: Opportunities for Translation"
985:
300:
292:
1116:
Studies on cultured malignant NK cells and/or patient tissue specimens find that numerous genes are
3650:
3434:
3404:
1909:
Goodlad JR (June 2017). "Epstein-Barr Virus-associated
Lymphoproliferative Disorders in the Skin".
1503:
1460:
1314:
1121:
466:
2551:"EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts"
4114:
2896:
2802:
2047:
2001:
1888:
1845:
1799:
1716:
1353:
and vincristine and therefore to CHOP and CHOP-like regimens. Subsequent studies discovered that
2628:
Yasuda H, Sugimoto K, Imai H, Isobe Y, Sasaki M, Kojima Y, Nakamura S, Oshimi K (January 2009).
1106:
and
Protein kinase B signaling pathways may also play a role in the pathogenesis of ENKTCL-NT.)
1280:. The disease may be incidentally diagnosed upon histopathology os sinus contents removed from
1003:
that when up-regulated in the cancer setting promotes these cells' invasiveness and to develop
4220:
4194:
3864:
3845:
3834:
3624:
3514:
3429:
3032:
2997:
2946:
2888:
2847:
2794:
2748:
2696:
2651:
2582:
2531:
2463:
2422:
2356:
2307:
2227:
2183:
2111:
2039:
2035:
1993:
1949:
1926:
1880:
1837:
1791:
1754:
1728:
1677:
1239:
1077:
that when up-regulated indirectly promotes the survival and proliferation of these cells; and
785:
329:
229:
143:
62:
3088:"PD-1 Blockade with Pembrolizumab in Relapsed/Refractory Mature T-cell and NK-cell Lymphomas"
3964:
3743:
3611:
3510:
3233:
3024:
2987:
2977:
2936:
2928:
2878:
2837:
2821:
2786:
2738:
2730:
2686:
2678:
2641:
2572:
2562:
2521:
2453:
2412:
2404:
2346:
2338:
2297:
2287:
2217:
2173:
2163:
2101:
2091:
2031:
1985:
1918:
1872:
1829:
1783:
1667:
1657:
1565:. Venetoclax is currently recruiting patients for a phase 2 clinical trial sponsored by the
1318:
628:
594:
539:
474:
370:
337:
203:
170:
1416:
Patients that have a complete or partial response to this regimen may then treated with an
3737:
3732:
3541:
3425:
3291:
3286:
1362:
996:
432:
280:
233:
2630:"Expression levels of apoptosis-related proteins and Ki-67 in nasal NK / T-cell lymphoma"
1715:
Mario L. Marques-Piubelli, M.D., Carlos A. Torres-Cabala, M.D., Roberto N. Miranda, M.D.
2331:
Philosophical
Transactions of the Royal Society of London. Series B, Biological Sciences
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2302:
2275:
2178:
2151:
2106:
2079:
1672:
1645:
1550:
1490:: The malignant cells in ~40% of ENKTCL-NT cases express the surface membrane protein,
1451:(PD-L1) is commonly overexpressed in ENKTCL-NT as an apparent result of EBV infection.
1437:
1433:
1338:
1125:
1097:
signaling pathway that in the cancer setting promotes cell survival and proliferation;
1043:
520:
437:
399:
3060:"Pilot Study of Pembrolizumab in Untreated Extranodal, NK/T Cell Lymphoma, Nasal Type"
2601:"CHPF2 chondroitin polymerizing factor 2 [Homo sapiens (human)] – Gene – NCBI"
469:
in the long (i.e. "q") arm at position 21–25 (notated as 6q21-25) from one of the two
4209:
4091:
3790:
3699:
3655:
3472:
3346:
2646:
2629:
2615:"MIR17HG miR-17-92a-1 cluster host gene [Homo sapiens (human)] – Gene – NCBI"
1528:
1452:
1378:
1342:
1322:
1103:
1047:
1039:
to promote these cell's survival and resistance to attack by the host immune system;
446:
390:
366:
17:
2900:
2051:
2005:
1892:
1849:
1803:
3694:
3356:
2806:
1542:
1495:
1477:
1410:
1406:
1354:
1334:
1310:
1306:
1059:
1055:
470:
2458:
2441:
1989:
1662:
1405:
Disseminated stage III and IV disease are treated with SMILE, i.e. dexamethasone,
130:, and extremely disfiguring lesions. However, ENKTCL-NT can also involve the eye,
3221:
2932:
2682:
2150:
de Mel S, Soon GS, Mok Y, Chung TH, Jeyasekharan AD, Chng WJ, Ng SB (June 2018).
3368:
1582:
1518:
1390:
1346:
1330:
1117:
1110:
1051:
955:
509:
394:
308:
257:
253:
221:
217:
188:
158:
3028:
2865:
Matnani R, Ganapathi KA, Lewis SK, Green PH, Alobeid B, Bhagat G (March 2017).
1922:
1833:
1702:
3264:
3199:
2790:
2292:
1787:
1484:
is recruiting individuals to examine the effects of Pembrolizmab on ENKTCL-NT.
1386:
1350:
1326:
1243:
1228:
1012:
604:
promotes cell proliferation, survival, migration, invasiveness, and metastasis
508:
and consequently divide into daughter cells which possess too few or too many
341:
304:
284:
122:
that commonly involves midline areas of the nasal cavity, oral cavity, and/or
67:
2567:
2096:
1876:
1553:
that indirectly promotes the activation of two apoptosis-inducing proteins,
1546:
1456:
1394:
1382:
1281:
798:
288:
178:
3036:
3001:
2950:
2892:
2851:
2798:
2752:
2700:
2655:
2614:
2586:
2535:
2467:
2426:
2360:
2342:
2311:
2231:
2187:
2115:
2043:
1997:
1930:
1884:
1841:
1795:
1681:
2842:
2825:
2600:
1273:
indolent T cell lymphoproliferative disorder of the gastrointestinal tract
4179:
4007:
3718:
3281:
3268:
2734:
2168:
1277:
1258:
is recommended to determine its involvement in this disorder. Whole body
1224:
1208:
1207:
On microscopic examination, involved tissues show commonly show areas of
1191:
1024:
992:
promotes these cells' proliferation and survival. They also overexpress:
981:
838:
599:
535:
419:
414:). LMP1 protein induces infected cells to overexpress genes that produce
407:
333:
296:
139:
127:
119:
71:
3182:
2982:
2408:
2222:
2205:
1626:
Epstein-Barr virus-associated extranodal NK/T cell lymphoma, nasal type
1533:
1527:: EBV-infected cells express the viral LMP1 and LMP2 proteins on their
1130:
1008:
918:
894:
863:
505:
382:
245:
162:
123:
2691:
2526:
2509:
1739:
Last author update: 5 January 2021. Last staff update: 14 October 2021
1432:
each case before treatment. The targets, therapeutic agents, and some
477:
genes (i.e. genes that protect cells from becoming malignant) such as
3727:
3194:
2883:
2866:
2719:"BCL-2 family proteins: changing partners in the dance towards death"
1349:, from its parent cells and thereby renders these cells resistant to
1259:
1162:
1028:
947:
935:
914:
850:
672:
353:
349:
345:
166:
131:
2777:
Suzuki R (February 2018). "NK/T Cell Lymphoma: Updates in Therapy".
307:; and/or hemophagocytosis, i.e. engulfment of blood cells by tissue
1436:(testing for appropriate dosages, safety, and side effects) and/or
3550:
3415:
3399:
2966:"Extranodal Natural Killer/T-Cell Lymphoma: An Incidental Finding"
1598:
1594:
1561:
thereby promoting cell death. It is approved for the treatment of
1448:
1150:
1146:
1138:
1134:
1074:
943:
939:
815:
642:
613:
494:
487:
483:
479:
249:
1749:
Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007).
1357:(NK cells do not express L-asaraginase) and, to a lesser extent,
328:
ENKTCL-NT is a disease of malignant NK or, very much less often,
4013:
3907:
3886:
3804:
3546:
3521:
3501:
3497:
3384:
3302:
3297:
1590:
1586:
1578:
1513:
1491:
1182:
1174:
1158:
1154:
1142:
1070:
that when up-regulated indirectly promotes these cells' growth;
1032:
963:
959:
951:
931:
927:
881:
751:
698:
580:
423:
415:
3237:
2080:"Novel Immunotherapy Options for Extranodal NK/T-Cell Lymphoma"
3753:
3748:
3638:
2440:
Jin Z, Wang Y, Wang J, Wu L, Pei R, Lai W, Wang Z (May 2018).
1644:
Takahara M, Kumai T, Kishibe K, Nagato T, Harabuchi Y (2021).
1573:
to evaluate its effects on refractory and recurrent ENKTCL-NT.
1212:
1170:
1166:
428:
398:
LMP-2A, and LMP-2B protein-producing genes; EBER-1 and EBER-2
386:
276:
126:
At these sites, the disease often takes the form of massive,
1420:
regimen, palliative chemotherapy, and/or experimental drugs.
311:
in the liver, spleen, bone morrow, and/or other tissues. or
271:
About 45% of patients present with elevated levels of serum
220:, and/or disfiguring, necrotic lesions of the nasal cavity,
3891:
Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
2022:
Farrell PJ (August 2018). "Epstein-Barr Virus and Cancer".
1944:
James, William D.; Berger, Timothy G.; et al. (2006).
2549:
Dojcinov SD, Fend F, Quintanilla-Martinez L (March 2018).
1011:
that result in daughter cells having too few or too many
151:
Epstein-Barr virus-associated lymphoproliferative disease
1195:
genes and/or the overexpression of the infected cells'
2510:"Frequent Mutations in Natural Killer/T Cell Lymphoma"
2325:
Shannon-Lowe C, Rickinson AB, Bell AI (October 2017).
2393:"Current treatment approaches for NK/T-cell lymphoma"
2276:"The diagnosis and management of NK/T-cell lymphomas"
3172:
2397:
Journal of Clinical and Experimental Hematopathology
2210:
Journal of Clinical and Experimental Hematopathology
1341:. This protein exports various molecules, including
776:, possibly promoting cell proliferation and survival
185:
Epstein-Barr virus-positive nodal NK/T cell lymphoma
4167:
4132:
4090:
4072:
4036:
4006:
3979:
3934:
3879:
3833:
3824:
3764:
3726:
3717:
3665:
3575:
3536:
3492:
3414:
3383:
3345:
3324:
3313:
3280:
3176:
1946:
Andrews' Diseases of the Skin: clinical Dermatology
897:
protein that regulates expression of other proteins
866:
protein that regulates expression of other proteins
77:
61:
37:
32:
3961:Peripheral T-cell lymphoma not otherwise specified
1822:Best Practice & Research. Clinical Haematology
1058:thereby rendering them resistant to this class of
844:correlates with advanced stage and poor prognosis
636:correlates with advanced stage and poor prognosis
607:correlates with advanced stage and poor prognosis
197:peripheral T-cell lymphoma not otherwise specified
3783:Precursor T acute lymphoblastic leukemia/lymphoma
3337:Precursor B acute lymphoblastic leukemia/lymphoma
2717:Kale J, Osterlund EJ, Andrews DW (January 2018).
2503:
2501:
2499:
2497:
2269:
2267:
2265:
2263:
2261:
2145:
1545:are a family of proteins that regulate cellular
1246:, are also commonly found in these infiltrates.
1223:as well the cytoplasmic intracellular proteins,
3527:Nodular lymphocyte predominant Hodgkin lymphoma
2772:
2770:
2768:
2766:
2764:
2762:
2712:
2710:
2495:
2493:
2491:
2489:
2487:
2485:
2483:
2481:
2479:
2477:
2386:
2384:
2382:
2380:
2378:
2376:
2374:
2372:
2370:
2259:
2257:
2255:
2253:
2251:
2249:
2247:
2245:
2243:
2241:
2199:
2197:
2143:
2141:
2139:
2137:
2135:
2133:
2131:
2129:
2127:
2125:
2073:
2071:
2069:
2067:
2065:
2063:
2061:
2017:
2015:
1971:
1969:
1967:
1965:
1904:
1902:
1815:
1813:
3917:Secondary cutaneous CD30+ large-cell lymphoma
3249:
1717:"Extranodal NK / T cell lymphoma, nasal type"
550:clinical impacts on the course of ENKTCL-NT:
8:
3607:Post-transplant lymphoproliferative disorder
3562:immunoproliferative immunoglobulin disorders
2508:Zhang Y, Li C, Xue W, Zhang M, Li Z (2018).
1733:: CS1 maint: multiple names: authors list (
1703:https://creativecommons.org/licenses/by/4.0/
1694:: CS1 maint: multiple names: authors list (
4120:Diffuse infiltrative lymphocytosis syndrome
2156:International Journal of Molecular Sciences
1440:(testing for efficacy and safety) include:
4159:Jessner lymphocytic infiltrate of the skin
3830:
3761:
3723:
3705:Primary cutaneous follicle center lymphoma
3450:Primary cutaneous follicle center lymphoma
3321:
3310:
3277:
3256:
3242:
3234:
3173:
841:to promote cell survival and prolifaration
48:
29:
2991:
2981:
2940:
2882:
2841:
2824:, Ferry JA, Zukerberg LR (January 2019).
2742:
2690:
2645:
2576:
2566:
2525:
2457:
2416:
2391:Yamaguchi M, Miyazaki K (December 2017).
2350:
2327:"Epstein-Barr virus-associated lymphomas"
2301:
2291:
2221:
2177:
2167:
2105:
2095:
2036:10.1146/annurev-pathmechdis-012418-013023
1671:
1661:
336:, which typically develop in and involve
110:polymorphic/malignant midline reticulosis
90:Extranodal NK/T-cell lymphoma, nasal type
3685:Primary cutaneous marginal zone lymphoma
3483:Primary cutaneous marginal zone lymphoma
1549:. Venetoclax (also termed ABT-199) is a
1001:serine/threonine-specific protein kinase
715:promotes cell proliferation and survival
690:promotes cell proliferation and survival
663:promotes cell proliferation and survival
552:
546:pro-malignant effects on EN/T cells and
4147:with bandlike and perivascular patterns
4109:Autoimmune lymphoproliferative syndrome
1636:
381:Infected cells carry ~10 cytosolic EBV
4226:Epstein–Barr virus–associated diseases
3956:Enteropathy-associated T-cell lymphoma
2830:American Journal of Clinical Pathology
2779:Current Hematologic Malignancy Reports
1726:
1687:
1470:Memorial Sloan Kettering Cancer Center
980:ENKTCL-NT malignant cells overexpress
4216:Lymphoid-related cutaneous conditions
1371:National Comprehensive Cancer Network
1367:European Society for Medical Oncology
633:lost ability to inhibit proliferation
7:
4104:X-linked lymphoproliferative disease
2514:Cellular Physiology and Biochemistry
2280:Journal of Hematology & Oncology
1418:autologous stem-cell transplantation
1413:is used in place of L-asparaginase.
1305:The treatment of ENKTCL- NT employs
709:JAK-STAT signaling pathway component
684:JAK-STAT signaling pathway component
521:Second generation sequencing methods
4060:Large granular lymphocytic leukemia
3680:Intravascular large B-cell lymphoma
2446:Hematology (Amsterdam, Netherlands)
1359:platinum-based antineoplastic drugs
1075:runt-related transcription factor 3
1559:Bcl-2 homologous antagonist killer
923:Hemophagocytic lymphohistiocytosis
262:hemophagocytic lymphohistiocytosis
25:
1313:. Early chemotherapies relied on
1035:which when up-regulated suppress
365:control mechanisms, particularly
2964:Althoff A, Bibliowicz M (2017).
2647:10.1111/j.1600-0609.2008.01152.x
1369:Clinical Practice guidelines or
3912:CD30+ cutaneous T-cell lymphoma
3129:Rouce, Rayne (8 January 2021).
2634:European Journal of Haematology
1265:Natural killer cell enteropathy
4142:Cutaneous lymphoid hyperplasia
4134:Cutaneous lymphoid hyperplasia
3993:Adult T-cell leukemia/lymphoma
3871:Adult T-cell leukemia/lymphoma
3810:Anaplastic large-cell lymphoma
3690:Primary cutaneous immunocytoma
3631:Splenic marginal zone lymphoma
2723:Cell Death and Differentiation
2555:Pathogens (Basel, Switzerland)
2274:Tse E, Kwong YL (April 2017).
1463:preparations that bind to the
1339:multidrug resistance protein 1
1095:platelet-derived growth factor
1044:multidrug resistance protein 1
157:of either one of two types of
149:ENKTCL-NT is classified as an
1:
4190:Lymphoproliferative disorders
4100:Lymphoproliferative disorders
4050:Extranodal NK-T-cell lymphoma
3922:Lymphomatoid papulosis type A
3901:Lymphomatoid papulosis type B
3815:Lymphomatoid papulosis type A
3675:Diffuse large B-cell lymphoma
2459:10.1080/10245332.2017.1385191
1990:10.1016/j.humpath.2018.05.020
1663:10.3390/microorganisms9071381
1577:Small molecule inhibitors of
1023:family of proteins including
797:inhibits BCL-5, may regulate
574:Clinical impact on ENKTCL-NT
527:mutation rates in ENKTCL-NT;
173:, that are infected with the
33:Extranodal NK-T-cell lymphoma
4082:Acute biphenotypic leukaemia
3971:Subcutaneous T-cell lymphoma
2933:10.1182/blood-2018-01-830968
2820:Xia D, Morgan EA, Berger D,
2683:10.1016/j.drudis.2017.05.009
1621:List of cutaneous conditions
1616:Subcutaneous T-cell lymphoma
1563:chronic lymphocytic leukemia
303:; decreased serum levels of
291:; increased serum levels of
4023:Aggressive NK-cell leukemia
3896:Pleomorphic T-cell lymphoma
3602:Lymphomatoid granulomatosis
3017:Current Medicinal Chemistry
1567:City of Hope Medical Center
313:aggressive NK-cell leukemia
266:aggressive NK-cell leukemia
4242:
3029:10.2174/092986711794839197
2024:Annual Review of Pathology
1923:10.1016/j.path.2017.01.001
1911:Surgical Pathology Clinics
1865:The Journal of Dermatology
1834:10.1016/j.beha.2018.07.002
1555:Bcl-2-associated X protein
1474:University of Pennsylvania
806:may increase cell survival
655:JAK-STAT signaling pathway
571:Influence on cell function
385:, i.e. gene-bearing viral
3276:
2791:10.1007/s11899-018-0430-5
2293:10.1186/s13045-017-0452-9
1788:10.1007/s11046-012-9559-2
1751:Dermatology: 2-Volume Set
1611:Cutaneous T-cell lymphoma
1571:National Cancer Institute
1276:progressed to aggressive
1082:programmed death-ligand 1
1068:histone methyltransferase
913:its product protein from
764:histone methyltransferase
226:Waldeyer's tonsillar ring
193:World Health Organization
56:
47:
4175:Hematological malignancy
4028:Blastic NK cell lymphoma
3856:Granulomatous slack skin
3612:Classic Hodgkin lymphoma
3511:Classic Hodgkin lymphoma
2568:10.3390/pathogens7010028
1269:lymphomatoid gastropathy
1111:Epigenetic abnormalities
774:cellular differentiation
730:MAX dimerization protein
155:malignant transformation
115:lethal midline granuloma
2097:10.3389/fonc.2018.00139
1877:10.1111/1346-8138.12322
1482:University of Hong Kong
1465:programmed cell death 1
1438:phase 2 clinical trials
1434:phase 1 clinical trials
1363:phase 3 clinical trials
1309:plus, where indicated,
1256:Bone marrow examination
1099:Notch signaling pathway
984:, a cellular signaling
443:notch signaling pathway
2871:Hematological Oncology
2343:10.1098/rstb.2016.0271
1498:/antineoplastic agent
1449:Program death-ligand 1
1190:gene for its miR-146a
1021:inhibitor of apoptosis
1005:chromosome segregation
502:chromosome segregation
410:-producing genes (see
402:-producing genes (see
242:gastrointestinal tract
238:gastrointestinal tract
136:gastrointestinal tract
102:nasal-type NK lymphoma
4054:Angiocentric lymphoma
3644:AIDS-related lymphoma
3468:Splenic marginal zone
2084:Frontiers in Oncology
1948:. Saunders Elsevier.
1234:in situ hybridization
1037:programmed cell death
293:liver-derived enzymes
273:lactate dehydrogenase
98:angiocentric lymphoma
18:Angiocentric lymphoma
4152:with nodular pattern
3851:Pagetoid reticulosis
3463:marginal zone B-cell
2735:10.1038/cdd.2017.186
2671:Drug Discovery Today
2169:10.3390/ijms19071931
2078:Hu B, Oki Y (2018).
1753:. St. Louis: Mosby.
986:transcription factor
406:); and certain BART
332:. Unlike most other
118:) is a rare type of
3651:Helicobacter pylori
3478:Nodal marginal zone
3405:Hairy cell leukemia
3271:and related disease
3118:. 18 December 2020.
2983:10.7759/cureus.1260
2843:10.1093/ajcp/aqy108
2409:10.3960/jslrt.17018
2223:10.3960/jslrt.51.21
1597:(e.g. WP1066), and
1551:small-molecule drug
1504:brentuximab vedotin
1461:monoclonal antibody
1288:Course of ENKTCL-NT
1219:, and cell surface
976:Overexpressed genes
831:/signaling pathways
453:Infected cell genes
404:EBV non-coding RNAs
367:immune surveillance
153:. It is due to the
4195:Lymphoid leukemias
4115:Leukemoid reaction
3951:Angioimmunoblastic
3617:Burkitt's lymphoma
3147:. 5 November 2019.
3104:. 31 October 2019.
2337:(1732): 20160271.
1721:Pathology Outlines
1427:Experimental drugs
1124:and therefore are
1088:Signaling pathways
766:, tumor suppressor
531:normal functions;
175:Epstein–Barr virus
106:NK/T-cell lymphoma
82:Epstein–Barr virus
4203:
4202:
4128:
4127:
4068:
4067:
4002:
4001:
3930:
3929:
3846:Mycosis fungoides
3713:
3712:
3571:
3570:
3515:Nodular sclerosis
3430:follicular B cell
3231:
3230:
2927:(20): 2262–2266.
2677:(10): 1466–1477.
2527:10.1159/000492835
2204:Kwong YL (2011).
1955:978-0-7216-2921-6
1760:978-1-4160-2999-1
1529:surface membranes
1240:white blood cells
910:
909:
791:BCL-6 corepressor
338:lymphatic tissues
330:cytotoxic T cells
232:, palate, and/or
230:paranasal sinuses
171:cytotoxic T cells
144:mycosis fungoides
87:
86:
27:Medical condition
16:(Redirected from
4233:
3965:Lennert lymphoma
3831:
3762:
3724:
3589:Primary effusion
3322:
3311:
3278:
3258:
3251:
3244:
3235:
3174:
3163:
3162:
3155:
3149:
3148:
3141:
3135:
3134:
3126:
3120:
3119:
3112:
3106:
3105:
3098:
3092:
3091:
3090:. 15 April 2019.
3084:
3078:
3077:
3070:
3064:
3063:
3056:
3050:
3047:
3041:
3040:
3012:
3006:
3005:
2995:
2985:
2961:
2955:
2954:
2944:
2911:
2905:
2904:
2886:
2884:10.1002/hon.2317
2862:
2856:
2855:
2845:
2817:
2811:
2810:
2774:
2757:
2756:
2746:
2714:
2705:
2704:
2694:
2666:
2660:
2659:
2649:
2625:
2619:
2618:
2611:
2605:
2604:
2597:
2591:
2590:
2580:
2570:
2546:
2540:
2539:
2529:
2505:
2472:
2471:
2461:
2437:
2431:
2430:
2420:
2388:
2365:
2364:
2354:
2322:
2316:
2315:
2305:
2295:
2271:
2236:
2235:
2225:
2201:
2192:
2191:
2181:
2171:
2147:
2120:
2119:
2109:
2099:
2075:
2056:
2055:
2019:
2010:
2009:
1973:
1960:
1959:
1941:
1935:
1934:
1906:
1897:
1896:
1860:
1854:
1853:
1817:
1808:
1807:
1771:
1765:
1764:
1746:
1740:
1738:
1732:
1724:
1712:
1706:
1699:
1693:
1685:
1675:
1665:
1641:
1593:(e.g. AZD1480),
1319:cyclophosphamide
1217:cytoplasmic CD3ε
736:tumor suppressor
625:tumor suppressor
595:tumor suppressor
553:
475:tumor suppressor
371:targeted therapy
324:Disease location
204:chemotherapeutic
52:
30:
21:
4241:
4240:
4236:
4235:
4234:
4232:
4231:
4230:
4206:
4205:
4204:
4199:
4163:
4124:
4086:
4074:
4064:
4032:
4011:
3998:
3975:
3936:
3926:
3875:
3820:
3768:
3766:
3741:
3736:
3730:
3709:
3661:
3567:
3544:
3532:
3488:
3426:germinal center
3410:
3379:
3341:
3317:
3315:
3295:
3290:
3284:
3272:
3262:
3232:
3227:
3226:
3185:
3171:
3166:
3161:. 7 April 2021.
3157:
3156:
3152:
3143:
3142:
3138:
3128:
3127:
3123:
3114:
3113:
3109:
3100:
3099:
3095:
3086:
3085:
3081:
3072:
3071:
3067:
3058:
3057:
3053:
3048:
3044:
3014:
3013:
3009:
2963:
2962:
2958:
2913:
2912:
2908:
2864:
2863:
2859:
2819:
2818:
2814:
2776:
2775:
2760:
2716:
2715:
2708:
2668:
2667:
2663:
2627:
2626:
2622:
2613:
2612:
2608:
2599:
2598:
2594:
2548:
2547:
2543:
2507:
2506:
2475:
2439:
2438:
2434:
2390:
2389:
2368:
2324:
2323:
2319:
2273:
2272:
2239:
2203:
2202:
2195:
2149:
2148:
2123:
2077:
2076:
2059:
2021:
2020:
2013:
1978:Human Pathology
1975:
1974:
1963:
1956:
1943:
1942:
1938:
1908:
1907:
1900:
1862:
1861:
1857:
1819:
1818:
1811:
1782:(5–6): 429–39.
1773:
1772:
1768:
1761:
1748:
1747:
1743:
1725:
1714:
1713:
1709:
1700:
1686:
1643:
1642:
1638:
1634:
1607:
1540:Bcl-2 proteins:
1429:
1303:
1290:
1252:
1205:
1118:hypermethylated
1114:
1090:
1019:members of the
997:aurora kinase A
978:
518:
464:
455:
433:B cell receptor
379:
362:
326:
321:
281:red blood cells
213:
169:variant termed
96:) (also termed
28:
23:
22:
15:
12:
11:
5:
4239:
4237:
4229:
4228:
4223:
4218:
4208:
4207:
4201:
4200:
4198:
4197:
4192:
4187:
4185:Leukemia cutis
4182:
4177:
4171:
4169:
4165:
4164:
4162:
4161:
4156:
4155:
4154:
4149:
4138:
4136:
4130:
4129:
4126:
4125:
4123:
4122:
4117:
4112:
4106:
4096:
4094:
4088:
4087:
4085:
4084:
4078:
4076:
4070:
4069:
4066:
4065:
4063:
4062:
4057:
4040:
4038:
4034:
4033:
4031:
4030:
4025:
4019:
4017:
4004:
4003:
4000:
3999:
3997:
3996:
3983:
3981:
3977:
3976:
3974:
3973:
3968:
3958:
3953:
3948:
3942:
3940:
3932:
3931:
3928:
3927:
3925:
3924:
3919:
3914:
3904:
3903:
3898:
3893:
3883:
3881:
3877:
3876:
3874:
3873:
3865:Sézary disease
3859:
3858:
3853:
3848:
3839:
3837:
3828:
3822:
3821:
3819:
3818:
3812:
3800:
3799:
3796:Prolymphocytic
3786:
3772:
3770:
3759:
3758:
3757:
3751:
3721:
3715:
3714:
3711:
3710:
3708:
3707:
3702:
3697:
3692:
3687:
3682:
3677:
3671:
3669:
3663:
3662:
3660:
3659:
3647:
3635:
3634:
3633:
3621:
3620:
3619:
3614:
3609:
3604:
3592:
3579:
3577:
3573:
3572:
3569:
3568:
3566:
3565:
3556:
3554:
3534:
3533:
3531:
3530:
3518:
3507:
3505:
3490:
3489:
3487:
3486:
3480:
3475:
3470:
3454:
3453:
3447:
3442:
3437:
3421:
3419:
3412:
3411:
3409:
3408:
3396:
3394:Prolymphocytic
3390:
3388:
3381:
3380:
3378:
3377:
3365:
3352:
3350:
3343:
3342:
3340:
3330:
3328:
3319:
3308:
3307:
3306:
3274:
3273:
3263:
3261:
3260:
3253:
3246:
3238:
3229:
3228:
3225:
3224:
3213:
3202:
3186:
3181:
3180:
3178:
3177:Classification
3170:
3169:External links
3167:
3165:
3164:
3150:
3136:
3121:
3107:
3093:
3079:
3065:
3062:. 12 May 2021.
3051:
3042:
3007:
2956:
2906:
2857:
2812:
2758:
2706:
2661:
2620:
2606:
2592:
2541:
2473:
2452:(4): 228–234.
2432:
2366:
2317:
2237:
2193:
2121:
2057:
2011:
1961:
1954:
1936:
1917:(2): 429–453.
1898:
1855:
1828:(3): 315–321.
1809:
1776:Mycopathologia
1766:
1759:
1741:
1707:
1650:Microorganisms
1635:
1633:
1630:
1629:
1628:
1623:
1618:
1613:
1606:
1603:
1575:
1574:
1543:Bcl-2 proteins
1537:
1522:
1507:
1485:
1428:
1425:
1424:
1423:
1422:
1421:
1403:
1402:
1401:
1355:L-asparaginase
1343:anthracyclines
1302:
1299:
1289:
1286:
1251:
1248:
1204:
1201:
1122:promoter sites
1113:
1108:
1089:
1086:
1048:anthracyclines
1007:errors during
977:
974:
908:
907:
904:
901:
898:
891:
888:
885:
877:
876:
873:
870:
867:
860:
857:
854:
846:
845:
842:
835:
832:
825:
822:
819:
811:
810:
807:
804:
801:
795:
792:
789:
781:
780:
777:
770:
767:
761:
758:
755:
747:
746:
743:
740:
737:
734:
731:
728:
720:
719:
716:
713:
710:
707:
704:
701:
695:
694:
691:
688:
685:
682:
679:
676:
668:
667:
664:
661:
658:
652:
649:
646:
638:
637:
634:
631:
626:
623:
620:
617:
609:
608:
605:
602:
597:
592:
589:
584:
576:
575:
572:
569:
566:
563:
560:
557:
517:
514:
504:errors during
463:
460:
454:
451:
438:interleukin 10
400:non-coding RNA
378:
375:
361:
358:
340:(particularly
325:
322:
320:
317:
212:
209:
85:
84:
79:
75:
74:
65:
59:
58:
54:
53:
45:
44:
39:
35:
34:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
4238:
4227:
4224:
4222:
4219:
4217:
4214:
4213:
4211:
4196:
4193:
4191:
4188:
4186:
4183:
4181:
4178:
4176:
4173:
4172:
4170:
4166:
4160:
4157:
4153:
4150:
4148:
4145:
4144:
4143:
4140:
4139:
4137:
4135:
4131:
4121:
4118:
4116:
4113:
4110:
4107:
4105:
4101:
4098:
4097:
4095:
4093:
4092:Lymphocytosis
4089:
4083:
4080:
4079:
4077:
4071:
4061:
4058:
4055:
4051:
4047:
4046:
4042:
4041:
4039:
4035:
4029:
4026:
4024:
4021:
4020:
4018:
4015:
4009:
4005:
3994:
3990:
3989:
3985:
3984:
3982:
3978:
3972:
3969:
3966:
3962:
3959:
3957:
3954:
3952:
3949:
3947:
3946:Hepatosplenic
3944:
3943:
3941:
3939:
3933:
3923:
3920:
3918:
3915:
3913:
3909:
3906:
3905:
3902:
3899:
3897:
3894:
3892:
3888:
3885:
3884:
3882:
3878:
3872:
3869:
3868:
3867:
3866:
3863:
3857:
3854:
3852:
3849:
3847:
3844:
3841:
3840:
3838:
3836:
3832:
3829:
3827:
3823:
3816:
3813:
3811:
3807:
3806:
3802:
3801:
3797:
3793:
3792:
3791:prolymphocyte
3788:
3787:
3784:
3780:
3776:
3773:
3771:
3763:
3760:
3755:
3752:
3750:
3747:
3746:
3745:
3739:
3734:
3729:
3725:
3722:
3720:
3716:
3706:
3703:
3701:
3700:Plasmacytosis
3698:
3696:
3693:
3691:
3688:
3686:
3683:
3681:
3678:
3676:
3673:
3672:
3670:
3668:
3664:
3657:
3656:MALT lymphoma
3653:
3652:
3648:
3645:
3641:
3640:
3636:
3632:
3629:
3628:
3627:
3626:
3622:
3618:
3615:
3613:
3610:
3608:
3605:
3603:
3600:
3599:
3598:
3597:
3593:
3590:
3586:
3585:
3581:
3580:
3578:
3574:
3564:
3563:
3558:
3557:
3555:
3552:
3548:
3543:
3539:
3535:
3528:
3524:
3523:
3519:
3516:
3512:
3509:
3508:
3506:
3503:
3499:
3495:
3491:
3484:
3481:
3479:
3476:
3474:
3471:
3469:
3465:
3464:
3460:
3459:marginal zone
3456:
3455:
3451:
3448:
3446:
3443:
3441:
3438:
3436:
3432:
3431:
3427:
3423:
3422:
3420:
3417:
3413:
3406:
3402:
3401:
3397:
3395:
3392:
3391:
3389:
3386:
3382:
3375:
3371:
3370:
3366:
3363:
3359:
3358:
3354:
3353:
3351:
3348:
3344:
3338:
3334:
3331:
3329:
3327:
3323:
3320:
3312:
3309:
3304:
3301:
3300:
3299:
3293:
3288:
3283:
3279:
3275:
3270:
3266:
3259:
3254:
3252:
3247:
3245:
3240:
3239:
3236:
3223:
3219:
3218:
3214:
3212:
3208:
3207:
3203:
3201:
3197:
3196:
3192:
3188:
3187:
3184:
3179:
3175:
3168:
3160:
3154:
3151:
3146:
3140:
3137:
3132:
3125:
3122:
3117:
3111:
3108:
3103:
3097:
3094:
3089:
3083:
3080:
3076:. 5 May 2021.
3075:
3069:
3066:
3061:
3055:
3052:
3046:
3043:
3038:
3034:
3030:
3026:
3023:(3): 439–81.
3022:
3018:
3011:
3008:
3003:
2999:
2994:
2989:
2984:
2979:
2975:
2971:
2967:
2960:
2957:
2952:
2948:
2943:
2938:
2934:
2930:
2926:
2922:
2918:
2910:
2907:
2902:
2898:
2894:
2890:
2885:
2880:
2876:
2872:
2868:
2861:
2858:
2853:
2849:
2844:
2839:
2835:
2831:
2827:
2823:
2816:
2813:
2808:
2804:
2800:
2796:
2792:
2788:
2784:
2780:
2773:
2771:
2769:
2767:
2765:
2763:
2759:
2754:
2750:
2745:
2740:
2736:
2732:
2728:
2724:
2720:
2713:
2711:
2707:
2702:
2698:
2693:
2688:
2684:
2680:
2676:
2672:
2665:
2662:
2657:
2653:
2648:
2643:
2639:
2635:
2631:
2624:
2621:
2616:
2610:
2607:
2602:
2596:
2593:
2588:
2584:
2579:
2574:
2569:
2564:
2560:
2556:
2552:
2545:
2542:
2537:
2533:
2528:
2523:
2519:
2515:
2511:
2504:
2502:
2500:
2498:
2496:
2494:
2492:
2490:
2488:
2486:
2484:
2482:
2480:
2478:
2474:
2469:
2465:
2460:
2455:
2451:
2447:
2443:
2436:
2433:
2428:
2424:
2419:
2414:
2410:
2406:
2403:(3): 98–108.
2402:
2398:
2394:
2387:
2385:
2383:
2381:
2379:
2377:
2375:
2373:
2371:
2367:
2362:
2358:
2353:
2348:
2344:
2340:
2336:
2332:
2328:
2321:
2318:
2313:
2309:
2304:
2299:
2294:
2289:
2285:
2281:
2277:
2270:
2268:
2266:
2264:
2262:
2260:
2258:
2256:
2254:
2252:
2250:
2248:
2246:
2244:
2242:
2238:
2233:
2229:
2224:
2219:
2215:
2211:
2207:
2200:
2198:
2194:
2189:
2185:
2180:
2175:
2170:
2165:
2161:
2157:
2153:
2146:
2144:
2142:
2140:
2138:
2136:
2134:
2132:
2130:
2128:
2126:
2122:
2117:
2113:
2108:
2103:
2098:
2093:
2089:
2085:
2081:
2074:
2072:
2070:
2068:
2066:
2064:
2062:
2058:
2053:
2049:
2045:
2041:
2037:
2033:
2029:
2025:
2018:
2016:
2012:
2007:
2003:
1999:
1995:
1991:
1987:
1983:
1979:
1972:
1970:
1968:
1966:
1962:
1957:
1951:
1947:
1940:
1937:
1932:
1928:
1924:
1920:
1916:
1912:
1905:
1903:
1899:
1894:
1890:
1886:
1882:
1878:
1874:
1870:
1866:
1859:
1856:
1851:
1847:
1843:
1839:
1835:
1831:
1827:
1823:
1816:
1814:
1810:
1805:
1801:
1797:
1793:
1789:
1785:
1781:
1777:
1770:
1767:
1762:
1756:
1752:
1745:
1742:
1736:
1730:
1722:
1718:
1711:
1708:
1704:
1697:
1691:
1683:
1679:
1674:
1669:
1664:
1659:
1655:
1651:
1647:
1640:
1637:
1631:
1627:
1624:
1622:
1619:
1617:
1614:
1612:
1609:
1608:
1604:
1602:
1600:
1596:
1592:
1588:
1584:
1580:
1572:
1568:
1564:
1560:
1556:
1552:
1548:
1544:
1541:
1538:
1535:
1530:
1526:
1523:
1520:
1515:
1511:
1508:
1505:
1501:
1497:
1493:
1489:
1486:
1483:
1479:
1475:
1471:
1466:
1462:
1458:
1454:
1453:Pembrolizumab
1450:
1446:
1443:
1442:
1441:
1439:
1435:
1426:
1419:
1415:
1414:
1412:
1408:
1404:
1399:
1398:
1396:
1392:
1388:
1384:
1380:
1379:dexamethasone
1376:
1375:
1374:
1372:
1368:
1364:
1360:
1356:
1352:
1348:
1344:
1340:
1336:
1332:
1328:
1324:
1323:anthracycline
1320:
1316:
1312:
1308:
1300:
1298:
1294:
1287:
1285:
1283:
1279:
1274:
1270:
1266:
1261:
1257:
1249:
1247:
1245:
1241:
1238:inflammatory
1236:
1235:
1230:
1226:
1222:
1218:
1214:
1210:
1202:
1200:
1198:
1193:
1189:
1185:
1184:
1180:
1176:
1172:
1168:
1164:
1160:
1156:
1152:
1148:
1144:
1140:
1136:
1132:
1127:
1123:
1119:
1112:
1109:
1107:
1105:
1104:VEGF receptor
1100:
1096:
1087:
1085:
1083:
1080:
1076:
1073:
1069:
1065:
1061:
1057:
1053:
1049:
1045:
1042:
1038:
1034:
1030:
1026:
1022:
1018:
1014:
1010:
1006:
1002:
998:
995:
991:
987:
983:
975:
973:
971:
967:
965:
961:
957:
953:
949:
945:
941:
937:
933:
929:
924:
920:
916:
905:
902:
899:
896:
892:
889:
886:
884:
883:
879:
878:
874:
871:
868:
865:
861:
858:
855:
853:
852:
848:
847:
843:
840:
836:
833:
830:
826:
823:
820:
818:
817:
813:
812:
808:
805:
802:
800:
796:
793:
790:
788:
787:
783:
782:
778:
775:
771:
768:
765:
762:
759:
756:
754:
753:
749:
748:
744:
741:
738:
735:
732:
729:
727:
726:
722:
721:
717:
714:
711:
708:
705:
702:
700:
697:
696:
692:
689:
686:
683:
680:
677:
675:
674:
670:
669:
665:
662:
659:
656:
653:
650:
647:
645:
644:
640:
639:
635:
632:
630:
627:
624:
621:
618:
616:
615:
611:
610:
606:
603:
601:
598:
596:
593:
590:
588:
585:
583:
582:
578:
577:
573:
570:
568:Mutation type
567:
564:
562:Mutation rate
561:
558:
555:
554:
551:
549:
545:
542:of activity;
541:
537:
534:
530:
526:
522:
516:Mutated genes
515:
513:
511:
507:
503:
498:
496:
491:
489:
485:
481:
476:
472:
468:
461:
459:
452:
450:
448:
447:immune system
444:
439:
434:
430:
425:
421:
417:
413:
412:EBV microRNAs
409:
405:
401:
396:
392:
388:
384:
376:
374:
372:
368:
359:
357:
355:
351:
347:
343:
339:
335:
331:
323:
318:
316:
314:
310:
306:
302:
301:triglycerides
298:
294:
290:
286:
282:
278:
274:
269:
267:
263:
259:
255:
251:
247:
243:
239:
235:
231:
227:
223:
219:
210:
208:
205:
200:
198:
194:
190:
186:
182:
180:
176:
172:
168:
164:
160:
156:
152:
147:
145:
141:
137:
133:
129:
125:
121:
117:
116:
111:
107:
103:
99:
95:
91:
83:
80:
76:
73:
69:
66:
64:
60:
55:
51:
46:
43:
40:
36:
31:
19:
4043:
3986:
3980:By infection
3861:
3860:
3842:
3803:
3789:
3767:development/
3695:Plasmacytoma
3649:
3637:
3623:
3594:
3582:
3576:By infection
3559:
3520:
3457:
3424:
3398:
3367:
3357:naive B cell
3355:
3316:development/
3215:
3204:
3189:
3153:
3139:
3124:
3110:
3096:
3082:
3068:
3054:
3049:add NCCN ref
3045:
3020:
3016:
3010:
2976:(5): e1260.
2973:
2969:
2959:
2924:
2920:
2909:
2874:
2870:
2860:
2836:(1): 75–85.
2833:
2829:
2815:
2782:
2778:
2729:(1): 65–80.
2726:
2722:
2674:
2670:
2664:
2640:(1): 39–45.
2637:
2633:
2623:
2609:
2595:
2558:
2554:
2544:
2517:
2513:
2449:
2445:
2435:
2400:
2396:
2334:
2330:
2320:
2283:
2279:
2213:
2209:
2159:
2155:
2087:
2083:
2027:
2023:
1981:
1977:
1945:
1939:
1914:
1910:
1871:(1): 29–39.
1868:
1864:
1858:
1825:
1821:
1779:
1775:
1769:
1750:
1744:
1720:
1710:
1690:cite journal
1653:
1649:
1639:
1576:
1539:
1525:EBV antigens
1524:
1509:
1500:auristatin E
1487:
1478:Philadelphia
1444:
1430:
1411:pegaspartase
1407:methotrexate
1335:prednisolone
1311:radiotherapy
1307:chemotherapy
1304:
1295:
1291:
1253:
1242:, including
1232:
1206:
1196:
1187:
1129:
1115:
1091:
1078:
1071:
1063:
1060:chemotherapy
1040:
1016:
993:
990:up-regulated
979:
969:
926:
911:
880:
849:
814:
784:
750:
723:
671:
641:
612:
579:
547:
543:
532:
528:
524:
519:
493:
478:
471:chromosome 6
465:
456:
393:rather than
380:
363:
327:
319:Pathogenesis
270:
254:night sweats
214:
211:Presentation
201:
184:
183:
148:
113:
109:
105:
101:
97:
93:
89:
88:
41:
3862:aggressive:
3835:MF+variants
3374:Mantle cell
3369:mantle zone
2877:(1): 3–16.
2785:(1): 7–12.
2520:(1): 1–16.
2216:(1): 21–8.
2162:(7): 1931.
1656:(7): 1381.
1583:tofacitinib
1519:Daratumumab
1391:carboplatin
1347:vincristine
1331:vincristine
1325:(primarily
1244:eosinophils
827:element in
510:chromosomes
462:Chromosomes
342:lymph nodes
309:histiocytes
258:weight loss
224:(including
222:nasopharynx
218:hard palate
189:lymph nodes
159:lymphocytes
38:Other names
4210:Categories
3938:peripheral
3435:Follicular
3265:Leukaemias
2692:1805/15547
1632:References
1387:ifosfamide
1351:adriamycin
1327:adriamycin
1229:granzyme B
1186:) and the
1056:Daunomycin
1052:Adriamycin
1013:chromosome
988:that when
968:(see) and
890:most cases
837:activates
305:fibrinogen
285:leukocytes
234:eye socket
68:Hematology
4073:Lymphoid+
3843:indolent:
3826:Cutaneous
3667:Cutaneous
3445:GCB DLBCL
3440:Burkitt's
3269:lymphomas
2822:Pinkus GS
2561:(1): 28.
2286:(1): 85.
2030:: 29–53.
1984:: 18–41.
1547:apoptosis
1457:Nivolumab
1395:cisplatin
1383:etopoxide
1301:Treatment
1284:surgery.
1282:sinusitis
1278:lymphomas
1250:Diagnosis
1203:Histology
1120:at their
829:TGF-β/BMP
799:apoptosis
657:component
467:Deletions
377:EBV genes
334:lymphomas
299:, and/or
289:platelets
287:, and/or
256:, and/or
94:ENKTCL-NT
63:Specialty
4221:Lymphoma
4180:leukemia
3738:leukemia
3733:lymphoma
3292:leukemia
3287:lymphoma
3037:21143116
3002:28652944
2951:29592893
2901:21364706
2893:27353398
2852:30212873
2799:29368155
2753:29149100
2701:28577912
2656:18778369
2587:29518976
2536:30134235
2468:28982299
2427:28679966
2361:28893938
2312:28410601
2232:21628857
2188:29966370
2116:29761078
2052:52051261
2044:30125149
2006:47010934
1998:29885408
1931:28477890
1893:42534926
1885:24438142
1850:52272644
1842:30213402
1804:14415645
1796:22744721
1729:cite web
1682:34202088
1605:See also
1569:and the
1225:perforin
1209:necrosis
1192:microRNA
1126:silenced
1066:EZH2, a
1050:such as
1025:survivin
972:((see).
966:, CHPF2,
906:unknown
875:unknown
809:unknown
779:unknown
772:reduces
745:unknown
718:unknown
693:unknown
666:unknown
565:Function
408:microRNA
383:episomes
297:ferritin
163:NK cells
140:lymphoma
134:, lung,
128:necrotic
120:lymphoma
72:Oncology
4168:General
4075:myeloid
4037:T or NK
4008:NK cell
3362:CLL/SLL
3222:D054391
3211:M9719/3
2993:5476476
2942:5958657
2807:3805195
2744:5729540
2578:5874754
2418:6144191
2352:5597738
2303:5391564
2179:6073933
2107:5937056
2090:: 139.
1673:8304202
1534:placebo
1496:cytoxic
1188:MIR146A
1131:BCL2L11
1062:drugs;
1009:mitosis
970:MIR17HG
919:alanine
903:unknown
895:SWI/SNF
872:unknown
864:SWI/SNF
742:unknown
559:Product
506:mitosis
391:latency
246:malaise
124:pharynx
4012:(most
3988:HTLV-1
3880:Non-MF
3769:marker
3742:(most
3728:T cell
3400:CD11c+
3318:marker
3296:(most
3282:B cell
3035:
3000:
2990:
2970:Cureus
2949:
2939:
2899:
2891:
2850:
2805:
2797:
2751:
2741:
2699:
2654:
2585:
2575:
2534:
2466:
2425:
2415:
2359:
2349:
2310:
2300:
2230:
2186:
2176:
2114:
2104:
2050:
2042:
2004:
1996:
1952:
1929:
1891:
1883:
1848:
1840:
1802:
1794:
1757:
1680:
1670:
1581:(e.g.
1389:, and
1333:, and
1317:(i.e.
1260:PET-CT
1181:, and
1031:, and
1029:Bcl-xL
936:ARID1A
915:valine
856:ARID1A
851:ARID1A
794:21–32%
678:STAT5B
673:STAT5B
622:12–20%
591:13–62%
540:losses
422:, and
354:B cell
350:T cell
346:spleen
179:latent
167:T cell
142:after
132:larynx
112:, and
78:Causes
3935:Other
3805:CD30+
3551:CD138
3522:CD20+
3416:CD79a
3206:ICD-O
3200:C86.0
2921:Blood
2897:S2CID
2803:S2CID
2048:S2CID
2002:S2CID
1889:S2CID
1846:S2CID
1800:S2CID
1599:DDX3X
1595:STAT3
1321:, an
1151:PRDM1
1147:SOCS6
1139:PTPN6
1135:DAPK1
982:NF-κB
944:ASXL3
940:EP300
839:NF-κB
821:ECSIT
816:ECSIT
760:7–80%
706:0–35%
681:~2–6%
651:8–26%
648:STAT3
643:STAT3
619:DDX3X
614:DDX3X
536:gains
495:PTPRK
488:FOXO3
484:PRDM1
480:HACE1
420:NF-κB
395:lytic
360:Genes
250:fever
165:or a
4014:CD56
3908:CD30
3887:CD30
3775:TdT+
3719:T/NK
3584:KSHV
3560:see
3547:CD38
3538:PCDs
3502:CD30
3498:CD15
3473:MALT
3385:CD22
3326:TdT+
3303:CD20
3298:CD19
3217:MeSH
3033:PMID
2998:PMID
2947:PMID
2889:PMID
2848:PMID
2795:PMID
2749:PMID
2697:PMID
2652:PMID
2583:PMID
2532:PMID
2464:PMID
2423:PMID
2357:PMID
2308:PMID
2228:PMID
2184:PMID
2112:PMID
2040:PMID
1994:PMID
1950:ISBN
1927:PMID
1881:PMID
1838:PMID
1792:PMID
1755:ISBN
1735:link
1696:link
1678:PMID
1591:JAK2
1587:JAK1
1579:JAK3
1557:and
1514:CD38
1510:CD38
1492:CD30
1488:CD30
1459:are
1455:and
1345:and
1315:CHOP
1221:CD56
1183:ASNS
1179:RARB
1175:MLH1
1159:HACE
1155:AIM1
1143:TET2
1054:and
1033:MCL1
999:, a
964:MGAM
960:IL6R
956:NARS
952:FAT4
932:MLL3
928:JAK1
900:loss
887:MCL1
882:MCL1
869:loss
859:4–8%
834:gain
803:loss
786:BCOR
769:loss
757:MLL2
752:MLL2
739:loss
712:gain
703:JAK3
699:JAK3
687:gain
660:gain
629:loss
600:gain
581:TP53
556:Gene
492:and
431:and
424:BCL2
416:cMyc
352:and
344:and
70:and
4045:EBV
3910:+:
3889:-:
3779:ALL
3754:CD8
3749:CD4
3744:CD3
3639:HIV
3625:HCV
3596:EBV
3500:+,
3347:CD5
3333:ALL
3191:ICD
3025:doi
2988:PMC
2978:doi
2937:PMC
2929:doi
2925:131
2879:doi
2838:doi
2834:151
2787:doi
2739:PMC
2731:doi
2687:hdl
2679:doi
2642:doi
2573:PMC
2563:doi
2522:doi
2454:doi
2413:PMC
2405:doi
2347:PMC
2339:doi
2335:372
2298:PMC
2288:doi
2218:doi
2174:PMC
2164:doi
2102:PMC
2092:doi
2032:doi
1986:doi
1919:doi
1873:doi
1830:doi
1784:doi
1780:174
1705:)."
1668:PMC
1658:doi
1585:),
1476:in
1445:PD1
1329:),
1213:CD2
1197:MYC
1171:p73
1167:p16
1163:p15
948:MSN
917:to
824:19%
733:~8%
725:MGA
587:p53
538:or
429:AKT
387:DNA
277:DNA
228:),
4212::
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3765:By
3553:+)
3549:+/
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