Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Hematologic Malignancy Reports
Published in: Current Hematologic Malignancy Reports 4/2018

01-08-2018 | T-Cell and Other Lymphoproliferative Malignancies (J Zain, Section Editor)

Pathogenesis of Enteropathy-Associated T Cell Lymphoma

Authors: Udit Chander, Rebecca J. Leeman-Neill, Govind Bhagat

Published in: Current Hematologic Malignancy Reports | Issue 4/2018

Login to get access

Abstract

Purpose of Review

To provide an update on the pathogenesis of enteropathy-associated T cell lymphoma (EATL) and its relationship with refractory celiac disease (RCD), in light of current knowledge of immune, genetic, and environmental factors that promote neoplastic transformation of intraepithelial lymphocytes (IELs).

Recent Findings

EATL frequently evolves from RCD type II (RCD II) but can occur “de novo” in individuals with celiac disease. Recurrent activating mutations in members of the JAK/STAT pathway have been recently described in EATL and RCD II, which suggests deregulation of cytokine signaling to be an early event in lymphomagenesis. Intraepithelial T cells are presumed to be the cell of origin of EATL (and RCD II). Recent in vitro molecular and phenotypic analyses and in vivo murine studies, however, suggest an origin of RCD II from innate IELs (NK/T cell precursors), which could also be the cell of origin of RCD II-derived EATL.

Summary

The immune microenvironment of the small intestinal mucosa in celiac disease fosters the development of EATL, often in a multistep pathway.
Literature
1.
CE SSH, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, et al. WHO classification of tumours and haematopoietic and lymphoid tissues. Revised 4th Edition ed. Lyon, France: IARC; 2017.
2.
3.
Isaacson P, Wright DH. Intestinal lymphoma associated with malabsorption. Lancet. 1978;1(8055):67–70.PubMedCrossRef
4.
Isaacson PG, O’Connor NT, Spencer J, Bevan DH, Connolly CE, Kirkham N, et al. Malignant histiocytosis of the intestine: a T-cell lymphoma. Lancet. 1985;2(8457):688–91.PubMedCrossRef
5.
Swerdlow SHCE, Harris NL, et al., editors. World Health Organization classification of tumors of haematopoietic and lymphoid tissues. Lyon, France: IARC; 2008.
6.
• Tack GJ, van Wanrooij RL, Langerak AW, Tjon JM, von Blomberg BM, Heideman DA, et al. Origin and immunophenotype of aberrant IEL in RCDII patients. Mol Immunol. 2012;50(4):262–70. Phenotypic and genotypic (TCR gene rearrangement) analysis of refractory celiac disease type II (RCD II) intraepithelial lymphocytes, which suggested an origin of RCD II from T/NK-cell precursors. PubMedCrossRef
7.
• Schmitz F, Tjon JM, Lai Y, Thompson A, Kooy-Winkelaar Y, Lemmers RJ, et al. Identification of a potential physiological precursor of aberrant cells in refractory coeliac disease type II. Gut. 2013;62(4):509–19. Phenotypic and gene expression analysis of innate intraepithelial lymphocytes and RCD II cell lines suggested a novel cell of origin of RCD II. PubMedCrossRef
8.
• Schmitz F, Tjon JM, van Bergen J, Koning F. Dendritic cells promote expansion and survival of aberrant TCR-negative intraepithelial lymphocyte lines from refractory celiac disease type II patients. Mol Immunol. 2014;58(1):10–6. Identification of selective stimulation of RCD II intraepithelial lymphocytes by dendritic cells in the absence of IL-15. PubMedCrossRef
9.
• Schmitz F, Kooy-Winkelaar Y, Wiekmeijer AS, Brugman MH, Mearin ML, Mulder C, et al. The composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment is altered in coeliac disease. Gut. 2016;65(8):1269–78. Comparative phenotypic and transcriptional analysis of RCD II intraepithelial lymphocytes and T cells revealed lack of differentiation potential of RCD II. PubMedCrossRef
10.
• Ettersperger J, Montcuquet N, Malamut G, Guegan N, Lopez-Lastra S, Gayraud S, et al. Interleukin-15-dependent T-cell-like innate intraepithelial lymphocytes develop in the intestine and transform into lymphomas in celiac disease. Immunity. 2016;45(3):610–25. In vivo and in vitro functional characterization of innate lymphocyte development to identify the cell of origin of RCD II and description of frequent JAK I and STAT3 mutations in RCD II. PubMedCrossRef
11.
• Kooy-Winkelaar YM, Bouwer D, Janssen GM, Thompson A, Brugman MH, Schmitz F, et al. CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes. Proc Natl Acad Sci U S A. 2017;114(6):E980–E9. Evidence that gliadin responsive CD4+ T cells in the lamina propria can communicate with and stimulate the proliferation and survival of innate intraepithelial lymphocytes in RCD II. PubMedPubMedCentralCrossRef
12.
• Roberti A, Dobay MP, Bisig B, Vallois D, Boechat C, Lanitis E, et al. Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations. Nat Commun. 2016;7:12602. Whole exome sequencing of MEITL (formerly EATL II) revealed frequent inactivating mutations and deletions of SETD2 that were absent in EATL (formerly EATL I), the latter showing frequent JAK1 and STAT3 mutations. PubMedPubMedCentralCrossRef
13.
• Nicolae A, Xi L, Pham TH, Pham TA, Navarro W, Meeker HG, et al. Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas. Leukemia. 2016;30(11):2245–7. Targeted next-generation sequencing of EATL, MEITL, and PTCL, NOS, identified overlapping spectrum of mutations in these entities. PubMedPubMedCentralCrossRef
14.
•• Moffitt AB, Ondrejka SL, McKinney M, Rempel RE, Goodlad JR, Teh CH, et al. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2. J Exp Med. 2017;214(5):1371–86. Whole exome sequencing of EATL and MEITL revealed overlapping spectrum of mutations, with both entities showing frequent recurrent mutations in SETD2 and members of the JAK-STAT signaling pathway. In vivo functional analysis of SETD2 loss using a mouse model revealed a role of SETD2 in T cell lineage specification. PubMedPubMedCentralCrossRef
15.
Chott A, Haedicke W, Mosberger I, Fodinger M, Winkler K, Mannhalter C, et al. Most CD56+ intestinal lymphomas are CD8+CD5-T-cell lymphomas of monomorphic small to medium size histology. Am J Pathol. 1998;153(5):1483–90.PubMedPubMedCentralCrossRef
16.
Delabie J, Holte H, Vose JM, Ullrich F, Jaffe ES, Savage KJ, et al. Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project. Blood. 2011;118(1):148–55.PubMedCrossRef
17.
A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The non-Hodgkin’s lymphoma classification project. Blood. 1997;89(11):3909–18.
18.
• Malamut G, Chandesris O, Verkarre V, Meresse B, Callens C, Macintyre E, et al. Enteropathy associated T cell lymphoma in celiac disease: a large retrospective study. Dig Liver Dis. 2013;45(5):377–84. Retrospective analysis highlighting different clinicopathogentic characteristics of RCD II-derived and de novo EATL. PubMedCrossRef
19.
Sieniawski M, Angamuthu N, Boyd K, Chasty R, Davies J, Forsyth P, et al. Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation. Blood. 2010;115(18):3664–70.PubMedCrossRef
20.
Verbeek WH, Van De Water JM, Al-Toma A, Oudejans JJ, Mulder CJ, Coupe VM. Incidence of enteropathy-associated T-cell lymphoma: a nation-wide study of a population-based registry in The Netherlands. Scand J Gastroenterol. 2008;43(11):1322–8.PubMedCrossRef
21.
Gale J, Simmonds PD, Mead GM, Sweetenham JW, Wright DH. Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center. J Clin Oncol. 2000;18(4):795–803.PubMedCrossRef
22.
O'Farrelly C, Feighery C, O'Briain DS, Stevens F, Connolly CE, McCarthy C, et al. Humoral response to wheat protein in patients with coeliac disease and enteropathy associated T cell lymphoma. Br Med J (Clin Res Ed). 1986;293(6552):908–10.PubMedCentralCrossRef
23.
Swinson CM, Slavin G, Coles EC, Booth CC. Coeliac disease and malignancy. Lancet. 1983;1(8316):111–5.PubMedCrossRef
24.
25.
Leffler DA, Green PH, Fasano A. Extraintestinal manifestations of coeliac disease. Nat Rev Gastroenterol Hepatol. 2015;12(10):561–71.PubMedCrossRef
26.
Howell WM, Leung ST, Jones DB, Nakshabendi I, Hall MA, Lanchbury JS, et al. HLA-DRB, -DQA, and -DQB polymorphism in celiac disease and enteropathy-associated T-cell lymphoma. Common features and additional risk factors for malignancy. Hum Immunol. 1995;43(1):29–37.PubMedCrossRef
27.
Corrao G, Corazza GR, Bagnardi V, Brusco G, Ciacci C, Cottone M, et al. Mortality in patients with coeliac disease and their relatives: a cohort study. Lancet. 2001;358(9279):356–61.PubMedCrossRef
28.
29.
Silano M, Volta U, Vincenzi AD, Dessi M, Vincenzi MD, Collaborating Centers of the Italian Registry of the Complications of Coeliac D. Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig Dis Sci. 2008;53(4):972–6.PubMedCrossRef
30.
Green PH, Fleischauer AT, Bhagat G, Goyal R, Jabri B, Neugut AI. Risk of malignancy in patients with celiac disease. Am J Med. 2003;115(3):191–5.PubMedCrossRef
31.
Catassi C, Bearzi I, Holmes GK. Association of celiac disease and intestinal lymphomas and other cancers. Gastroenterology. 2005;128(4 Suppl 1):S79–86.PubMedCrossRef
32.
Sharaiha RZ, Lebwohl B, Reimers L, Bhagat G, Green PH, Neugut AI. Increasing incidence of enteropathy-associated T-cell lymphoma in the United States, 1973–2008. Cancer. 2012;118(15):3786–92.PubMedCrossRef
33.
Askling J, Linet M, Gridley G, Halstensen TS, Ekstrom K, Ekbom A. Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis. Gastroenterology. 2002;123(5):1428–35.PubMedCrossRef
34.
Catassi C, Fabiani E, Corrao G, Barbato M, De Renzo A, Carella AM, et al. Risk of non-Hodgkin lymphoma in celiac disease. JAMA. 2002;287(11):1413–9.PubMedCrossRef
35.
Leonard JN, Tucker WF, Fry JS, Coulter CA, Boylston AW, McMinn RM, et al. Increased incidence of malignancy in dermatitis herpetiformis. Br Med J (Clin Res Ed). 1983;286(6358):16–8.CrossRef
36.
37.
Cottone M, Termini A, Oliva L, Magliocco A, Marrone C, Orlando A, et al. Mortality and causes of death in celiac disease in a Mediterranean area. Dig Dis Sci. 1999;44(12):2538–41.PubMedCrossRef
38.
Gao Y, Kristinsson SY, Goldin LR, Bjorkholm M, Caporaso NE, Landgren O. Increased risk for non-Hodgkin lymphoma in individuals with celiac disease and a potential familial association. Gastroenterology. 2009;136(1):91–8.PubMedCrossRef
39.
Ilus T, Kaukinen K, Virta LJ, Huhtala H, Maki M, Kurppa K, et al. Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease. Aliment Pharmacol Ther. 2014;39(4):418–25.PubMedCrossRef
40.
Ilyas M, Niedobitek G, Agathanggelou A, Barry RE, Read AE, Tierney R, et al. Non-Hodgkin’s lymphoma, coeliac disease, and Epstein-Barr virus: a study of 13 cases of enteropathy-associated T- and B-cell lymphoma. J Pathol. 1995;177(2):115–22.PubMedCrossRef
41.
Daum S, Ullrich R, Heise W, Dederke B, Foss HD, Stein H, et al. Intestinal non-Hodgkin’s lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin’s Lymphoma. J Clin Oncol. 2003;21(14):2740–6.PubMedCrossRef
42.
Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology. 2001;120(3):636–51.PubMedCrossRef
43.
Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013;62(1):43–52.PubMedCrossRef
44.
45.
Jewell DP. Ulcerative enteritis. Br Med J (Clin Res Ed). 1983;287(6407):1740–1.CrossRef
46.
West J. Celiac disease and its complications: a time traveller’s perspective. Gastroenterology. 2009;136(1):32–4.PubMedCrossRef
47.
Wright DH, Jones DB, Clark H, Mead GM, Hodges E, Howell WM. Is adult-onset coeliac disease due to a low-grade lymphoma of intraepithelial T lymphocytes? Lancet. 1991;337(8754):1373–4.PubMedCrossRef
48.
Alfsen GC, Beiske K, Bell H, Marton PF. Low-grade intestinal lymphoma of intraepithelial T lymphocytes with concomitant enteropathy-associated T cell lymphoma: case report suggesting a possible histogenetic relationship. Hum Pathol. 1989;20(9):909–13.PubMedCrossRef
49.
Isaacson P, Wright DH. Malignant histiocytosis of the intestine. Its relationship to malabsorption and ulcerative jejunitis. Hum Pathol. 1978;9(6):661–77.PubMedCrossRef
50.
Cellier C, Delabesse E, Helmer C, Patey N, Matuchansky C, Jabri B, et al. Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group Lancet. 2000;356(9225):203–8.
51.
Murray A, Cuevas EC, Jones DB, Wright DH. Study of the immunohistochemistry and T cell clonality of enteropathy-associated T cell lymphoma. Am J Pathol. 1995;146(2):509–19.PubMedPubMedCentral
52.
Ashton-Key M, Diss TC, Pan L, Du MQ, Isaacson PG. Molecular analysis of T-cell clonality in ulcerative jejunitis and enteropathy-associated T-cell lymphoma. Am J Pathol. 1997;151(2):493–8.PubMedPubMedCentral
53.
Bagdi E, Diss TC, Munson P, Isaacson PG. Mucosal intra-epithelial lymphocytes in enteropathy-associated T-cell lymphoma, ulcerative jejunitis, and refractory celiac disease constitute a neoplastic population. Blood. 1999;94(1):260–4.PubMed
54.
Carbonnel F, Grollet-Bioul L, Brouet JC, Teilhac MF, Cosnes J, Angonin R, et al. Are complicated forms of celiac disease cryptic T-cell lymphomas? Blood. 1998;92(10):3879–86.PubMed
55.
Daum S, Weiss D, Hummel M, Ullrich R, Heise W, Stein H, et al. Frequency of clonal intraepithelial T lymphocyte proliferations in enteropathy-type intestinal T cell lymphoma, coeliac disease, and refractory sprue. Gut. 2001;49(6):804–12.PubMedPubMedCentralCrossRef
56.
Cellier C, Patey N, Mauvieux L, Jabri B, Delabesse E, Cervoni JP, et al. Abnormal intestinal intraepithelial lymphocytes in refractory sprue. Gastroenterology. 1998;114(3):471–81.PubMedCrossRef
57.
Malamut G, Afchain P, Verkarre V, Lecomte T, Amiot A, Damotte D, et al. Presentation and long-term follow-up of refractory celiac disease: comparison of type I with type II. Gastroenterology. 2009;136(1):81–90.PubMedCrossRef
58.
Al-Toma A, Verbeek WH, Hadithi M, von Blomberg BM, Mulder CJ. Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience. Gut. 2007;56(10):1373–8.PubMedPubMedCentralCrossRef
59.
Rubio-Tapia A, Kelly DG, Lahr BD, Dogan A, Wu TT, Murray JA. Clinical staging and survival in refractory celiac disease: a single center experience. Gastroenterology. 2009;136(1):99–107. quiz 352-3 PubMedCrossRef
60.
Roshan B, Leffler DA, Jamma S, Dennis M, Sheth S, Falchuk K, et al. The incidence and clinical spectrum of refractory celiac disease in a north American referral center. Am J Gastroenterol. 2011;106(5):923–8.PubMedCrossRef
61.
Daum S, Cellier C, Mulder CJ. Refractory coeliac disease. Best Pract Res Clin Gastroenterol. 2005;19(3):413–24.PubMedCrossRef
62.
Verkarre V, Asnafi V, Lecomte T, Patey Mariaud-de Serre N, Leborgne M, Grosdidier E, et al. Refractory coeliac sprue is a diffuse gastrointestinal disease. Gut. 2003;52(2):205–11.PubMedPubMedCentralCrossRef
63.
Verbeek WH, Goerres MS, von Blomberg BM, Oudejans JJ, Scholten PE, Hadithi M, et al. Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease. Clin Immunol. 2008;126(1):48–56.PubMedCrossRef
64.
Leffler DA, Dennis M, Hyett B, Kelly E, Schuppan D, Kelly CP. Etiologies and predictors of diagnosis in nonresponsive celiac disease. Clin Gastroenterol Hepatol. 2007;5(4):445–50.PubMedCrossRef
65.
O’Mahony S, Howdle PD, Losowsky MS. Review article: management of patients with non-responsive coeliac disease. Aliment Pharmacol Ther. 1996;10(5):671–80.PubMedCrossRef
66.
Arguelles-Grande C, Brar P, Green PH, Bhagat G. Immunohistochemical and T-cell receptor gene rearrangement analyses as predictors of morbidity and mortality in refractory celiac disease. J Clin Gastroenterol. 2013;47(7):593–601.PubMedCrossRef
67.
Daum S, Ipczynski R, Schumann M, Wahnschaffe U, Zeitz M, Ullrich R. High rates of complications and substantial mortality in both types of refractory sprue. Eur J Gastroenterol Hepatol. 2009;21(1):66–70.PubMedCrossRef
68.
Vader W, Stepniak D, Kooy Y, Mearin L, Thompson A, van Rood JJ, et al. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. Proc Natl Acad Sci U S A. 2003;100(21):12390–5.PubMedPubMedCentralCrossRef
69.
Al-Toma A, Goerres MS, Meijer JW, Pena AS, Crusius JB, Mulder CJ. Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma. Clin Gastroenterol Hepatol. 2006;4(3):315–9.PubMedCrossRef
70.
Dubois PC, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A, et al. Multiple common variants for celiac disease influencing immune gene expression. Nat Genet. 2010;42(4):295–302.PubMedPubMedCentralCrossRef
71.
Trynka G, Hunt KA, Bockett NA, Romanos J, Mistry V, Szperl A, et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat Genet. 2011;43(12):1193–201.PubMedPubMedCentralCrossRef
72.
Kumar V, Wijmenga C, Withoff S. From genome-wide association studies to disease mechanisms: celiac disease as a model for autoimmune diseases. Semin Immunopathol. 2012;34(4):567–80.PubMedPubMedCentralCrossRef
73.
Castellanos-Rubio A, Fernandez-Jimenez N, Kratchmarov R, Luo X, Bhagat G, Green PH, et al. A long noncoding RNA associated with susceptibility to celiac disease. Science. 2016;352(6281):91–5.PubMedPubMedCentralCrossRef
74.
75.
Meresse B, Malamut G, Cerf-Bensussan N. Celiac disease: an immunological jigsaw. Immunity. 2012;36(6):907–19.PubMedCrossRef
76.
77.
Jarry A, Cerf-Bensussan N, Brousse N, Selz F, Guy-Grand D. Subsets of CD3+ (T cell receptor alpha/beta or gamma/delta) and CD3- lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood. Eur J Immunol. 1990;20(5):1097–103.PubMedCrossRef
78.
Calleja S, Vivas S, Santiuste M, Arias L, Hernando M, Nistal E, et al. Dynamics of non-conventional intraepithelial lymphocytes—NK, NKT, and gammadelta T—in celiac disease: relationship with age, diet, and histopathology. Dig Dis Sci. 2011;56(7):2042–9.PubMedCrossRef
79.
Eiras P, Leon F, Camarero C, Lombardia M, Roldan E, Bootello A, et al. Intestinal intraepithelial lymphocytes contain a CD3- CD7+ subset expressing natural killer markers and a singular pattern of adhesion molecules. Scand J Immunol. 2000;52(1):1–6.PubMedCrossRef
80.
Leon F, Roldan E, Sanchez L, Camarero C, Bootello A, Roy G. Human small-intestinal epithelium contains functional natural killer lymphocytes. Gastroenterology. 2003;125(2):345–56.PubMedCrossRef
81.
82.
83.
Spencer J, Cerf-Bensussan N, Jarry A, Brousse N, Guy-Grand D, Krajewski AS, et al. Enteropathy-associated T cell lymphoma (malignant histiocytosis of the intestine) is recognized by a monoclonal antibody (HML-1) that defines a membrane molecule on human mucosal lymphocytes. Am J Pathol. 1988;132(1):1–5.PubMedPubMedCentral
84.
Lambolez F, Mayans S, Cheroutre H. Lymphocytes: intraepithelial. eLS. Hoboken: John Wiley & Sons, Ltd; 2001.
85.
Tjon JM, Verbeek WH, Kooy-Winkelaar YM, Nguyen BH, van der Slik AR, Thompson A, et al. Defective synthesis or association of T-cell receptor chains underlies loss of surface T-cell receptor-CD3 expression in enteropathy-associated T-cell lymphoma. Blood. 2008;112(13):5103–10.PubMedCrossRef
86.
Jaffe ESAD, Campo E, Harris NL, Quintanilla-Fend L. Hematopathology. 2nd Edition ed. Philadelphia. USA: Elsevier; 2016.
87.
Attygalle AD, Cabecadas J, Gaulard P, Jaffe ES, de Jong D, Ko YH, et al. Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward—report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology. Histopathology. 2014;64(2):171–99.PubMedCrossRef
88.
Chan JK, Chan AC, Cheuk W, Wan SK, Lee WK, Lui YH, et al. Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent gammadelta T-cell receptor expression. Am J Surg Pathol. 2011;35(10):1557–69.PubMedCrossRef
89.
90.
Abadie V, Sollid LM, Barreiro LB, Jabri B. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu Rev Immunol. 2011;29:493–525.PubMedCrossRef
91.
Hollon JR, Cureton PA, Martin ML, Puppa EL, Fasano A. Trace gluten contamination may play a role in mucosal and clinical recovery in a subgroup of diet-adherent non-responsive celiac disease patients. BMC Gastroenterol. 2013;13:40.PubMedPubMedCentralCrossRef
92.
Malamut G, Meresse B, Cellier C, Cerf-Bensussan N. Refractory celiac disease: from bench to bedside. Semin Immunopathol. 2012;34(4):601–13.PubMedCrossRef
93.
Hue S, Mention JJ, Monteiro RC, Zhang S, Cellier C, Schmitz J, et al. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity. 2004;21(3):367–77.PubMedCrossRef
94.
Meresse B, Chen Z, Ciszewski C, Tretiakova M, Bhagat G, Krausz TN, et al. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity. 2004;21(3):357–66.PubMedCrossRef
95.
Meresse B, Curran SA, Ciszewski C, Orbelyan G, Setty M, Bhagat G, et al. Reprogramming of CTLs into natural killer-like cells in celiac disease. J Exp Med. 2006;203(5):1343–55.PubMedPubMedCentralCrossRef
96.
Benahmed M, Meresse B, Arnulf B, Barbe U, Mention JJ, Verkarre V, et al. Inhibition of TGF-beta signaling by IL-15: a new role for IL-15 in the loss of immune homeostasis in celiac disease. Gastroenterology. 2007;132(3):994–1008.PubMedCrossRef
97.
Ben Ahmed M, Belhadj Hmida N, Moes N, Buyse S, Abdeladhim M, Louzir H, et al. IL-15 renders conventional lymphocytes resistant to suppressive functions of regulatory T cells through activation of the phosphatidylinositol 3-kinase pathway. J Immunol. 2009;182(11):6763–70.PubMedCrossRef
98.
Mention JJ, Ben Ahmed M, Begue B, Barbe U, Verkarre V, Asnafi V, et al. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology. 2003;125(3):730–45.PubMedCrossRef
99.
Malamut G, El Machhour R, Montcuquet N, Martin-Lanneree S, Dusanter-Fourt I, Verkarre V, et al. IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis. J Clin Invest. 2010;120(6):2131–43.PubMedPubMedCentralCrossRef
100.
Tjon JM, Kooy-Winkelaar YM, Tack GJ, Mommaas AM, Schreurs MW, Schilham MW, et al. DNAM-1 mediates epithelial cell-specific cytotoxicity of aberrant intraepithelial lymphocyte lines from refractory celiac disease type II patients. J Immunol. 2011;186(11):6304–12.PubMedCrossRef
101.
Rothenberg EV, Ungerback J, Champhekar A. Forging T-lymphocyte identity: intersecting networks of transcriptional control. Adv Immunol. 2016;129:109–74.PubMedCrossRef
102.
Verkarre V, Romana SP, Cellier C, Asnafi V, Mention JJ, Barbe U, et al. Recurrent partial trisomy 1q22-q44 in clonal intraepithelial lymphocytes in refractory celiac sprue. Gastroenterology. 2003;125(1):40–6.PubMedCrossRef
103.
Baumgartner AK, Zettl A, Chott A, Ott G, Muller-Hermelink HK, Starostik P. High frequency of genetic aberrations in enteropathy-type T-cell lymphoma. Lab Investig. 2003;83(10):1509–16.PubMedCrossRef
104.
• Deleeuw RJ, Zettl A, Klinker E, Haralambieva E, Trottier M, Chari R, et al. Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes. Gastroenterology. 2007;132(5):1902–11. Array-based genomic analysis and HLA genotyping showed differences and similarities of genomic changes in EATL (formerly EATL I) and MEITL (formerly EATL II). PubMedCrossRef
105.
Zettl A, Ott G, Makulik A, Katzenberger T, Starostik P, Eichler T, et al. Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma. Am J Pathol. 2002;161(5):1635–45.PubMedPubMedCentralCrossRef
106.
Obermann EC, Diss TC, Hamoudi RA, Munson P, Wilkins BS, Camozzi ML, et al. Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy-type T-cell lymphoma. J Pathol. 2004;202(2):252–62.PubMedCrossRef
107.
Chen J, Zhang Y, Petrus MN, Xiao W, Nicolae A, Raffeld M, et al. Cytokine receptor signaling is required for the survival of ALK- anaplastic large cell lymphoma, even in the presence of JAK1/STAT3 mutations. Proc Natl Acad Sci U S A. 2017;114(15):3975–80.PubMedPubMedCentralCrossRef
108.
Mazzarella G, Stefanile R, Camarca A, Giliberti P, Cosentini E, Marano C, et al. Gliadin activates HLA class I-restricted CD8+ T cells in celiac disease intestinal mucosa and induces the enterocyte apoptosis. Gastroenterology. 2008;134(4):1017–27.PubMedPubMedCentralCrossRef
109.
Han A, Newell EW, Glanville J, Fernandez-Becker N, Khosla C, Chien YH, et al. Dietary gluten triggers concomitant activation of CD4+ and CD8+ alphabeta T cells and gammadelta T cells in celiac disease. Proc Natl Acad Sci U S A. 2013;110(32):13073–8.PubMedPubMedCentralCrossRef
110.
Fina D, Sarra M, Caruso R, Del Vecchio Blanco G, Pallone F, MacDonald TT, et al. Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease. Gut. 2008;57(7):887–92.PubMedCrossRef
111.
Bodd M, Raki M, Tollefsen S, Fallang LE, Bergseng E, Lundin KE, et al. HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. Mucosal Immunol. 2010;3(6):594–601.PubMedCrossRef
112.
Colpitts SL, Stoklasek TA, Plumlee CR, Obar JJ, Guo C, Lefrancois L. Cutting edge: the role of IFN-alpha receptor and MyD88 signaling in induction of IL-15 expression in vivo. J Immunol. 2012;188(6):2483–7.PubMedPubMedCentralCrossRef
113.
Bouziat R, Hinterleitner R, Brown JJ, Stencel-Baerenwald JE, Ikizler M, Mayassi T, et al. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science. 2017;356(6333):44–50.PubMedPubMedCentralCrossRef
114.
Kim SM, Mayassi T, Jabri B. Innate immunity: actuating the gears of celiac disease pathogenesis. Best Pract Res Clin Gastroenterol. 2015;29(3):425–35.PubMedPubMedCentralCrossRef
115.
Cejkova P, Zettl A, Baumgartner AK, Chott A, Ott G, Muller-Hermelink HK, et al. Amplification of NOTCH1 and ABL1 gene loci is a frequent aberration in enteropathy-type T-cell lymphoma. Virchows Arch. 2005;446(4):416–20.PubMedCrossRef
116.
Nairismagi ML, Tan J, Lim JQ, Nagarajan S, Ng CC, Rajasegaran V, et al. JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma. Leukemia. 2016;30(6):1311–9.PubMedPubMedCentralCrossRef
Metadata
Title
Pathogenesis of Enteropathy-Associated T Cell Lymphoma
Authors
Udit Chander
Rebecca J. Leeman-Neill
Govind Bhagat
Publication date
01-08-2018
Publisher
Springer US
Published in
Current Hematologic Malignancy Reports / Issue 4/2018
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-018-0459-5

Other articles of this Issue 4/2018

Current Hematologic Malignancy Reports 4/2018 Go to the issue

Stem Cell Transplantation (R Maziarz, Section Editor)

Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia; Current Evidence, and Improving Outcomes Going Forward

Myelodysplastic Syndromes (M Savona, Section Editor)

Disordered Immune Regulation and its Therapeutic Targeting in Myelodysplastic Syndromes

Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)

Updates in the Pathology of Precursor Lymphoid Neoplasms in the Revised Fourth Edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues

Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)

Recent Advances in the Biology and Treatment of T Cell Acute Lymphoblastic Leukemia

T-Cell and Other Lymphoproliferative Malignancies (J Zain, Section Editor)

Molecular Insights Into Pathogenesis of Peripheral T Cell Lymphoma: a Review

Health Economics (N Khera, Section Editor)

Economic Impact of Oral Therapies for Chronic Lymphocytic Leukemia—the Burden of Novelty
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits