Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Acute lymphoblastic leukemia

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

Leukemia volume 34, pages 1730–1740 (2020)Cite this article

Subjects

Abstract

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 (IL7Rpmut) T-ALL were slow-responders, with a high rate of M2/M3 day-8 marrow compared with IL7Rp non-mutated (IL7RpWT) T-ALL (p = 0.002) and minimal residual disease positivity at 6-weeks (MRD1) (p = 0.008) but no difference in MRD2 positivity at 12-weeks. Despite this, no adverse prognosis was evidenced when censored for allogeneic hematopoietic stem cell transplantation (HSCT). In time-dependent analysis, HSCT did not benefit IL7Rpmut patients whereas it was of marked benefit to IL7RpWT cases. IL7Rp-mutations identify a subgroup of slow-responder T-ALLs which benefit from post-induction chemotherapy regimens but not from HSCT. Our data suggest that prior knowledge of the mutation status of IL7Rp may influence HSCT decision and help to guide therapy reduction.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: IL7R signaling pathway genes mutational landscape in adult T-ALL enrolled in the GRAALL-2003 and -2005 protocols.
Fig. 2: Genetic profiles of adult IL7Rpmut T-ALL.
Fig. 3: Adult IL7Rpmut T-ALLs are not associated with poor prognosis.
Fig. 4: Adult high-risk IL7Rpmut T-ALL displayed favorable outcome treated by chemotherapy and did not benefit from HSCT.

Similar content being viewed by others

References

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

    CAS  PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  4. 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.

    CAS  PubMed  Google Scholar 

  5. 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  Google Scholar 

  6. 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.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  8. 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.

    CAS  PubMed  Google Scholar 

  9. 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  Google Scholar 

  10. 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  PubMed Central  Google Scholar 

  11. 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.

    CAS  PubMed  Google Scholar 

  12. 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.

    CAS  PubMed  Google Scholar 

  13. 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  Google Scholar 

  14. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 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  Google Scholar 

  16. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  18. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 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.

    CAS  PubMed  Google Scholar 

  20. 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  Google Scholar 

  21. 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  Google Scholar 

  22. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 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  PubMed Central  Google Scholar 

  25. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 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.

    CAS  PubMed  Google Scholar 

  28. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 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.

    CAS  PubMed  Google Scholar 

  30. 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.

    CAS  PubMed  Google Scholar 

  31. 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.

    CAS  PubMed  Google Scholar 

  32. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 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  Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  36. 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.

    Google Scholar 

  37. 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.

    CAS  PubMed  Google Scholar 

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

    Google Scholar 

  39. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 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.

    CAS  PubMed  Google Scholar 

  41. 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.

    CAS  PubMed  Google Scholar 

  42. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 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.

    CAS  PubMed  Google Scholar 

  44. 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.

    CAS  PubMed  Google Scholar 

  45. 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  Google Scholar 

  46. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 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.

    CAS  PubMed  Google Scholar 

  48. 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.

  49. 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.

    CAS  PubMed  Google Scholar 

  50. 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.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the participants in the GRAALL-2003 and GRAALL-2005 study groups for the collection and the provision of data and patient samples, and Véronique Lheritier for the collection of clinical data. We thank the Swiss State Secretariat for Education, Research and Innovation (SERI) Switzerland for support. We thank Force Hemato and Association pour la Recherche contre le Cancer (ARC) for support. We acknowledge Guillaume Andrieu, Emmanuelle Clappier, André Delannoy, and Philippe Rousselot for their support in editing the manuscript.

Author information

Authors and Affiliations

  1. Université de Paris, Institut Necker-Enfants Malades, Institut National de Recherche Médicale U1151, Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France

    Rathana Kim, Aurore Touzart, Florian Thonier, Patrick Villarese, Loïc Passini, Elizabeth Macintyre, Vahid Asnafi & Ludovic Lhermitte

  2. Université de Paris, EA-3518, Institut de Recherche Saint-Louis, Hematology Adolescent and Young Adult Unit, Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Paris, France

    Nicolas Boissel

  3. Department of Hematology, CHU de Bordeaux, Hôpital du Haut-Levêque, Pessac, France

    Thibaut Leguay

  4. Department of Hematology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France

    Xavier Thomas

  5. Université de Paris, Department of Hematology, Adult Hematology Unit, Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Paris, France

    Emmanuel Raffoux & Hervé Dombret

  6. Service d’Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France

    Françoise Huguet

  7. Plateforme Bioinformatique, Institut Imagine, Paris, France

    Cécile Fourrage

  8. Department of Hematology, CHU Angers, Angers, France

    Mathilde Hunault & Norbert Ifrah

  9. CRCINA, INSERM Université de Nantes, Université d’Angers, Angers, France

    Mathilde Hunault

  10. Inserm U1245 and Department of Hematology, Centre Henri Becquerel and Normandie Univ UNIROUEN, Rouen, France

    Stéphane Lepretre

  11. Department of Hematology, CHU, Nantes, France

    Patrice Chevallier

  12. INSERM UMR1232 & CNRS ERL6001 CRCINA IRS-UN, Nantes, France

    Patrice Chevallier

  13. Institut Universitaire d’Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris Cancer Research Institute (PACRI), Paris, France

    Thorsten Braun

  14. Laboratoire de Transfert des Leucémies, EA3518, Université de Paris, Paris, France

    Thorsten Braun

  15. Département d’Hématologie, Assistance Publique - Hôpitaux de Paris, Hôpital Avicenne, Université Paris 13, Bobigny, France

    Thorsten Braun

  16. Group for Research on Adult Acute Lymphoblastic Leukemia, Coordination Office, Centre Hospitalier Lyon Sud, Pierre Bénite, France

    Véronique Lhéritier

  17. Institut d’Hématologie de Basse-Normandie, CHU, Caen, France

    Sylvain Chantepie

  18. Service d’Hématologie, Assistance Publique, Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France

    Sébastien Maury

  19. Service d’Hématologie Clinique, CHU, Hôpital Pontchaillou, Rennes, France

    Martine Escoffre

  20. Service d’Hématologie, Institut de Cancérologie Lucien Neuwirth, Saint Priest en Jarez, France

    Emmanuelle Tavernier

  21. Department of Oncology, Department of Medical Specialties, University Hospital and University of Geneva, Geneva, Switzerland

    Yves Chalandon

  22. Swiss Group for Clinical Cancer Research, Bern, Switzerland

    Yves Chalandon

  23. Université Catholique de Louvain, Service d’Hématologie, CHU UCL Namur—Godinne, Yvoir, Belgique

    Carlos Graux

Authors
  1. Rathana Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicolas Boissel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aurore Touzart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thibaut Leguay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Florian Thonier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xavier Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Emmanuel Raffoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Françoise Huguet
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Patrick Villarese
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Cécile Fourrage
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Loïc Passini
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mathilde Hunault
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Stéphane Lepretre
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Patrice Chevallier
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Thorsten Braun
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Véronique Lhéritier
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Sylvain Chantepie
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Sébastien Maury
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Martine Escoffre
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Emmanuelle Tavernier
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Yves Chalandon
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Carlos Graux
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Elizabeth Macintyre
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Norbert Ifrah
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Vahid Asnafi
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Hervé Dombret
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Ludovic Lhermitte
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf the GRAALL group

Contributions

Conception and design: RK, LL, and NB. Collection and assembly of data: all authors. Data analysis and interpretation: RK, LL, NB, VL, HD, and VA. Manuscript writing: all authors.

Corresponding author

Correspondence to Ludovic Lhermitte.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, R., Boissel, N., Touzart, A. et al. Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation. Leukemia 34, 1730–1740 (2020). https://doi.org/10.1038/s41375-019-0685-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-019-0685-4

This article is cited by

Search

Advanced search

Quick links