Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation.

Adolescent Adult Biomarkers, Tumor / genetics Female Follow-Up Studies Gene Expression Regulation, Neoplastic Hematopoietic Stem Cell Transplantation / mortality Humans Male Middle Aged Mutation Neoplasm, Residual / genetics Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics Prognosis Receptors, Interleukin-7 / genetics Survival Rate Transplantation, Homologous Young Adult

Journal

Leukemia

ISSN: 1476-5551

Titre abrégé: Leukemia

Pays: England

ID NLM: 8704895

Informations de publication

Date de publication:
07 2020

Historique:

received: 12 07 2019

accepted: 05 12 2019

revised: 17 11 2019

pubmed: 30 1 2020

medline: 28 10 2020

entrez: 30 1 2020

Statut: ppublish

Résumé

The prognostic value of IL7-receptor pathway (IL7Rp) mutations in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. We performed a comprehensive study of 200 adult patients with T-ALL included in the GRAALL2003/2005 protocols to address the clinical significance of IL7Rp mutations. Next-generation sequencing of the IL7Rp (IL7R/JAK1/JAK3/STAT5B) revealed that IL7Rp mutations were frequent in adult T-ALL (28%) particularly in immature/early T-cell progenitor (ETP)-ALL. They were associated with mutations of NOTCH-pathway, PHF6, and PRC2 components but not with K/NRAS. IL7Rp mutated (IL7Rp

Identifiants

DOI: 10.1038/s41375-019-0685-4 PMID: 31992840

pubmed: 31992840

doi: 10.1038/s41375-019-0685-4

pii: 10.1038/s41375-019-0685-4

doi:

Substances chimiques

Biomarkers, Tumor 0

Receptors, Interleukin-7 0

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1730-1740

Références

Aifantis I, Raetz E, Buonamici S. Molecular pathogenesis of T-cell leukaemia and lymphoma. Nat Rev Immunol. 2008;8:380–90.

pubmed: 18421304 pmcid: 18421304

Van Vlierberghe P, Ferrando A. The molecular basis of T cell acute lymphoblastic leukemia. J Clin Investig. 2012;122:3398–406.

pubmed: 23023710

Girardi T, Vicente C, Cools J, De Keersmaecker K. The genetics and molecular biology of T-ALL. Blood. 2017;129:1113–23.

pubmed: 28115373 pmcid: 5363819

Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008;111:1827–33.

pubmed: 18048644

Gökbuget N, Kneba M, Raff T, Trautmann H, Bartram C-R, Arnold R, et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120:1868–76.

pubmed: 22442346

Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, Lambert J, Beldjord K, Lengliné E, et al. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. J Clin Oncol. 2013;31:4333–42.

pubmed: 24166518

Marks DI, Rowntree C. Management of adults with T-cell lymphoblastic leukemia. Blood. 2017;129:1134–42.

pubmed: 28115371

Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland M-L, Leguay T, et al. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014;123:3739–49.

pubmed: 24740809

Gökbuget N, Stanze D, Beck J, Diedrich H, Horst H-A, Hüttmann A, et al. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012;120:2032–41.

pubmed: 22493293

Desjonquères A, Chevallier P, Thomas X, Huguet F, Leguay T, Bernard M, et al. Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study. Blood Cancer J. 2016;6:e504.

pubmed: 27935576 pmcid: 5223147

Breit S, Stanulla M, Flohr T, Schrappe M, Ludwig W-D, Tolle G, et al. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood. 2006;108:1151–7.

pubmed: 16614245

Asnafi V, Buzyn A, Le Noir S, Baleydier F, Simon A, Beldjord K, et al. NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study. Blood. 2009;113:3918–24.

pubmed: 19109228

Pui C-H, Carroll WL, Meshinchi S, Arceci RJ. Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J Clin Oncol. 2011;29:551–65.

pubmed: 21220611

Pui C-H, Mullighan CG, Evans WE, Relling MV. Pediatric acute lymphoblastic leukemia: where are we going and how do we get there? Blood. 2012;120:1165–74.

pubmed: 22730540 pmcid: 3418713

Dhédin N, Huynh A, Maury S, Tabrizi R, Beldjord K, Asnafi V, et al. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood. 2015;125:2486–96.quiz 2586.

pubmed: 25587040

Durum SK, Candèias S, Nakajima H, Leonard WJ, Baird AM, Berg LJ, et al. Interleukin 7 receptor control of T cell receptor gamma gene rearrangement: role of receptor-associated chains and locus accessibility. J Exp Med. 1998;188:2233–41.

pubmed: 9858510 pmcid: 2212428

Mazzucchelli R, Durum SK. Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol. 2007;7:144–54.

pubmed: 17259970

Boudil A, Matei IR, Shih H-Y, Bogdanoski G, Yuan JS, Chang SG, et al. IL-7 coordinates proliferation, differentiation and TCRA recombination during thymocyte β-selection. Nat Immunol. 2015;16:397–405.

pubmed: 25729925 pmcid: 4368453

Tal N, Shochat C, Geron I, Bercovich D, Izraeli S. Interleukin 7 and thymic stromal lymphopoietin: from immunity to leukemia. Cell Mol Life Sci. 2014;71:365–78.

pubmed: 23625073

De Keersmaecker K, Atak ZK, Li N, Vicente C, Patchett S, Girardi T, et al. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nat Genet. 2013;45:186–90.

pubmed: 23263491

Neumann M, Vosberg S, Schlee C, Heesch S, Schwartz S, Gökbuget N, et al. Mutational spectrum of adult T-ALL. Oncotarget. 2015;6:2754–66.

pubmed: 25595890

Vicente C, Schwab C, Broux M, Geerdens E, Degryse S, Demeyer S, et al. Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia. Haematologica. 2015;100:1301–10.

pubmed: 26206799 pmcid: 4591762

Gianfelici V, Chiaretti S, Demeyer S, Di Giacomo F, Messina M, La Starza R, et al. RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications. Haematologica. 2016;101:941–50.

pubmed: 27151993 pmcid: 4967573

Li Y, Buijs-Gladdines JGCAM, Canté-Barrett K, Stubbs AP, Vroegindeweij EM, Smits WK, et al. IL-7 receptor mutations and steroid resistance in pediatric T cell acute lymphoblastic leukemia: a genome sequencing study. PLoS Med. 2016;13:e1002200.

pubmed: 27997540 pmcid: 5172551

Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017;49:1211–8.

pubmed: 28671688 pmcid: 5535770

Zenatti PP, Ribeiro D, Li W, Zuurbier L, Silva MC, Paganin M, et al. Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia. Nat Genet. 2011;43:932–9.

pubmed: 21892159 pmcid: 7424552

Degryse S, de Bock CE, Cox L, Demeyer S, Gielen O, Mentens N, et al. JAK3 mutants transform hematopoietic cells through JAK1 activation, causing T-cell acute lymphoblastic leukemia in a mouse model. Blood. 2014;124:3092–100.

pubmed: 25193870

Maude SL, Dolai S, Delgado-Martin C, Vincent T, Robbins A, Selvanathan A, et al. Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia. Blood. 2015;125:1759–67.

pubmed: 25645356 pmcid: 4357583

Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009;27:911–8.

pubmed: 19124805

Huguet F, Chevret S, Leguay T, Thomas X, Boissel N, Escoffre-Barbe M, et al. Intensified therapy of acute lymphoblastic leukemia in adults: report of the randomized GRAALL-2005 clinical trial. J Clin Oncol. 2018;36:2514–23.

pubmed: 29863974

Bergeron J, Clappier E, Radford I, Buzyn A, Millien C, Soler G, et al. Prognostic and oncogenic relevance of TLX1/HOX11 expression level in T-ALLs. Blood. 2007;110:2324–30.

pubmed: 17609427

Bond J, Marchand T, Touzart A, Cieslak A, Trinquand A, Sutton L, et al. An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. Haematologica. 2016;101:732–40.

pubmed: 26944475 pmcid: 5013941

van der Velden VHJ, Cazzaniga G, Schrauder A, Hancock J, Bader P, Panzer-Grumayer ER, et al. Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia. 2007;21:604–11.

pubmed: 17287850

Cox DR. Regression models and life-tables. J R Stat Soc Ser B Methodol. 1972;34:187–220.

Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika. 1994;81:515–26.

Mantel N, Byar DP. Evaluation of response-time data involving transient states: an illustration using heart-transplant data. J Am Stat Assoc. 1974;69:81–6.

Simon R, Makuch RW. A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to responder versus non-responder bias. Stat Med. 1984;3:35–44.

pubmed: 6729287

Andersen PK, Gill RD. Cox’s regression model for counting processes: a large sample study. Ann Stat. 1982;10:1100–20.

Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, et al. Circos: an information aesthetic for comparative genomics. Genome Res. 2009;19:1639–45.

pubmed: 19541911 pmcid: 2752132

Shochat C, Tal N, Gryshkova V, Birger Y, Bandapalli OR, Cazzaniga G, et al. Novel activating mutations lacking cysteine in type I cytokine receptors in acute lymphoblastic leukemia. Blood. 2014;124:106–10.

pubmed: 24787007

Macintyre EA, Smit L, Ritz J, Kirsch IR, Strominger JL. Disruption of the SCL locus in T-lymphoid malignancies correlates with commitment to the T-cell receptor alpha beta lineage. Blood. 1992;80:1511–20.

pubmed: 1387813

Gutierrez A, Kentsis A, Sanda T, Holmfeldt L, Chen S-C, Zhang J, et al. The BCL11B tumor suppressor is mutated across the major molecular subtypes of T-cell acute lymphoblastic leukemia. Blood. 2011;118:4169–73.

pubmed: 21878675 pmcid: 3204734

Tremblay CS, Brown FC, Collett M, Saw J, Chiu SK, Sonderegger SE, et al. Loss-of-function mutations of Dynamin 2 promote T-ALL by enhancing IL-7 signalling. Leukemia. 2016;30:1993–2001.

pubmed: 27118408

Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grümayer R, Möricke A, et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011;118:2077–84.

pubmed: 21719599

O’Connor D, Enshaei A, Bartram J, Hancock J, Harrison CJ, Hough R, et al. Genotype-specific minimal residual disease interpretation improves stratification in pediatric acute lymphoblastic leukemia. J Clin Oncol. 2018;36:34–43.

pubmed: 29131699

Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, et al. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009;114:5136–45.

pubmed: 2792210 pmcid: 2792210

Baak U, Gökbuget N, Orawa H, Schwartz S, Hoelzer D, Thiel E, et al. Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group. Leukemia. 2008;22:1154–60.

pubmed: 18368072

Degryse S, de Bock CE, Demeyer S, Govaerts I, Bornschein S, Verbeke D, et al. Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia. Leukemia. 2017. https://doi.org/10.1038/leu.2017.276 .

Asnafi V, Beldjord K, Boulanger E, Comba B, Le Tutour P, Estienne M-H, et al. Analysis of TCR, pT alpha, and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment. Blood. 2003;101:2693–703.

pubmed: 12446444

Pongers-Willemse MJ, Verhagen OJ, Tibbe GJ, Wijkhuijs AJ, de Haas V, Roovers E, et al. Real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia using junctional region specific TaqMan probes. Leukemia. 1998;12:2006–14.

pubmed: 9844931