Current Hematologic Malignancy Reports

, Volume 13, Issue 4, pp 265–274 | Cite as

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

  • Mehrdad Hefazi
  • Mark R. LitzowEmail author
Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Acute Lymphocytic Leukemias


Purpose of Review

This article provides an overview of the current knowledge regarding the biology and treatment of T cell acute lymphoblastic leukemia (T-ALL) and highlights the most recent findings in this field over the past 5 years.

Recent Findings

Remarkable progress has been made in the genomic landscape of T-ALL over the past few years. The discovery of activating mutations of NOTCH1 and FBXW7 in a majority of patients has been a seminal observation, with several early phase clinical trials currently exploring these as potential therapeutic targets. Characterization of early T cell precursor ALL, incorporation of minimal residual disease assessment into therapeutic protocols, and use of pediatric-intensive regimens along with judicious use of allogeneic HCT have significantly improved risk stratification and treatment outcomes.


Improved risk stratification and the use of novel targeted therapies based on recent genomic discoveries are expected to change the therapeutic landscape of T-ALL and hopefully improve the outcomes of this historically poor prognosis disease.


T cell acute lymphoblastic leukemia Early T cell precursor acute lymphoblastic leukemia Minimal residual disease Nelarabine Targeted therapies 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001–2007. Blood. 2012;119:34–43. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Arber DA, Orazi A, Hasserjian R, Borowitz MJ, Le Beau MM, Bloomfield CD, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–406.CrossRefPubMedGoogle Scholar
  3. 3.
    Litzow MR, Ferrando AA. How I treat T-cell acute lymphoblastic leukemia in adults. Blood. 2015;126:833–41. Available from: CrossRefPubMedGoogle Scholar
  4. 4.
    Bazarbachi A, Suarez F, Fields P, Hermine O. How I treat adult T-cell leukemia/lymphoma. Blood. 2011;118:1736–45. Available from: CrossRefPubMedGoogle Scholar
  5. 5.
    Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9:1783–6. Available from: PubMedGoogle Scholar
  6. 6.
    Vitale A, Guarini A, Ariola C, Mancini M, Mecucci C, Cuneo A, et al. Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol. Blood. 2006;107:473–9. Available from: CrossRefPubMedGoogle Scholar
  7. 7.
    Jain N, Lamb AV, O’Brien S, Ravandi F, Konopleva M, Jabbour E, et al. Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. Blood. 2016;127:1863–9. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10:147–56. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012;481:157–63. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Haydu JE, Ferrando AA. Early T-cell precursor acute lymphoblastic leukaemia. Curr Opin Hematol. 2013;20:369–73.CrossRefPubMedGoogle Scholar
  11. 11.
    Belver L, Ferrando A. The genetics and mechanisms of T cell acute lymphoblastic leukaemia. Nat Rev Cancer. 2016;16:494–507.Nature Publishing Group. Scholar
  12. 12.
    Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991;66:649–61. Available from: CrossRefPubMedGoogle Scholar
  13. 13.
    Weng AP, Ferrando AA, Lee W, Morris JP, Silverman LB, Sanchez-Irizarry C, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science (80-). 2004;306:269–71. Available from: CrossRefGoogle Scholar
  14. 14.
    O’Neil J, Grim J, Strack P, Rao S, Tibbitts D, Winter C, et al. FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med. 2007;204:1813–24. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, Margolin A, et al. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci U S A. 2006;103:18261–6. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    • 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. Detailed genome-wide sequencing of a large cohort of T-ALL. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    • 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. Blood. 2009;114:5136–45. The impact of biology, CNS involvement, and donor availability on T-ALL outcomes in a large prospective study. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    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. Available from: CrossRefPubMedGoogle Scholar
  19. 19.
    Zuurbier L, Homminga I, Calvert V, te Winkel ML, Buijs-Gladdines JGCAM, Kooi C, et al. NOTCH1 and/or FBXW7 mutations predict for initial good prednisone response but not for improved outcome in pediatric T-cell acute lymphoblastic leukemia patients treated on DCOG or COALL protocols. Leukemia. 2010;24:2014–22. Available from: CrossRefPubMedGoogle Scholar
  20. 20.
    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. Available from: CrossRefPubMedGoogle Scholar
  21. 21.
    Clappier E, Collette S, Grardel N, Girard S, Suarez L, Brunie G, et al. NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951. Leukemia. 2010;24:2023–31. Available from: CrossRefPubMedGoogle Scholar
  22. 22.
    Deftos ML, He YW, Ojala EW, Bevan MJ. Correlating notch signaling with thymocyte maturation. Immunity. 1998;9:777–86. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Real PJ, Ferrando AA. NOTCH inhibition and glucocorticoid therapy in T-cell acute lymphoblastic leukemia. Leukemia. 2009;23:1374–7. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    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. Available from: CrossRefPubMedGoogle Scholar
  25. 25.
    Inukai T, Kiyokawa N, Campana D, Coustan-Smith E, Kikuchi A, Kobayashi M, et al. Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children’s Cancer Study Group Study L99–15. Br J Haematol. 2012;156:358–65. Available from: CrossRefPubMedGoogle Scholar
  26. 26.
    Ma M, Wang X, Tang J, Xue H, Chen J, Pan C, et al. Early T-cell precursor leukemia: a subtype of high risk childhood acute lymphoblastic leukemia. Front Med. 2012;6:416–20. Available from: CrossRefPubMedGoogle Scholar
  27. 27.
    Patrick K, Wade R, Goulden N, Mitchell C, Moorman AV, Rowntree C, et al. Outcome for children and young people with early T-cell precursor acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003. Br J Haematol. 2014;166:421–4. Available from: CrossRefPubMedGoogle Scholar
  28. 28.
    Bernt KM, Hunger SP, Neff T. The Functional role of PRC2 in early T-cell precursor acute lymphoblastic leukemia (ETP-ALL)— mechanisms and opportunities. Front Pediatr. 2016;4:49. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Van Vlierberghe P, Ambesi-Impiombato A, De Keersmaecker K, Hadler M, Paietta E, Tallman MS, et al. Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia. Blood. 2013;122:74–82. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Brüggemann M, Raff T, Flohr T, Gökbuget N, Nakao M, Droese J, et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006;107:1116–23. Available from: CrossRefPubMedGoogle Scholar
  31. 31.
    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. Available from: CrossRefPubMedGoogle Scholar
  32. 32.
    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. Available from: CrossRefPubMedGoogle Scholar
  33. 33.
    Teachey DT, Hunger SP. Predicting relapse risk in childhood acute lymphoblastic leukaemia. Br J Haematol. 2013;162:606–20. Available from: CrossRefPubMedGoogle Scholar
  34. 34.
    • 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. Available from: Different kinetics and impact of MRD on T-ALL outcomes. CrossRefPubMedGoogle Scholar
  35. 35.
    Brent L. Wood, Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Si Chen, Barbara Asselin, Natia Esiashvili, Mignon L. Loh, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz SPH. T-lymphoblastic leukemia (T-ALL) shows excellent outcome, lack of significance of the early Thymic precursor (ETP) Immunophenotype, and validation of the prognostic value of end-induction minimal residual disease (MRD) in Children’s oncology group (COG) Study AALL0434 Blood 2014;124.Google Scholar
  36. 36.
    Wood BL, Winter SS, Dunsmore KP, Devidas M, Chen S, Asselin B, et al. Patients with early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) have high levels of minimal residual disease (MRD) at the end of induction—a Children’s oncology group (COG) study [abstract]. Blood. 2009;114Google Scholar
  37. 37.
    Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood. 2002;99:863–71. Available from: CrossRefPubMedGoogle Scholar
  38. 38.
    Lauer SJ, Pinkel D, Buchanan GR, Sartain P, Cornet JM, Krance R, et al. Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia. Cancer. 1987;60:2366–71. Available from: CrossRefPubMedGoogle Scholar
  39. 39.
    Clavell LA, Gelber RD, Cohen HJ, Hitchcock-Bryan S, Cassady JR, Tarbell NJ, et al. Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. N Engl J Med. 1986;315:657–63. Available from: CrossRefPubMedGoogle Scholar
  40. 40.
    Linker CA, Levitt LJ, O’Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood. 1991;78:2814–22. Available from: PubMedGoogle Scholar
  41. 41.
    • Hoelzer D, Thiel E, Arnold R, Beck J, Beelen DW, Bornhäuser M, et al. Successful subtype oriented treatment strategies in adult T-all; results of 744 patients treated in three consecutive GMALL studies. Blood. 2009;114:324. The imrpovement in T-ALL outcomes in three consecutive trials after the incorporation of pegasperginases into the treatment. Google Scholar
  42. 42.
    Rosen O, Müller HJ, Gökbuget N, Langer W, Peter N, Schwartz S, et al. Pegylated asparaginase in combination with high-dose methotrexate for consolidation in adult acute lymphoblastic leukaemia in first remission: a pilot study. Br J Haematol. 2003;123:836–41. Available from: CrossRefPubMedGoogle Scholar
  43. 43.
    Kozlowski P, Åström M, Ahlberg L, Bernell P, Hulegårdh E, Hägglund H, et al. High relapse rate of T cell acute lymphoblastic leukemia in adults treated with hyper-CVAD chemotherapy in Sweden. Eur J Haematol. 2014;92:377–81. Available from: CrossRefPubMedGoogle Scholar
  44. 44.
    Patel B, Kirkwood AA, Dey A, Marks DI, McMillan AK, Menne TF, et al. Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial. Leukemia. 2017;31:58–64. Available from: CrossRefPubMedGoogle Scholar
  45. 45.
    DeAngelo DJ, Stevenson KE, Dahlberg SE, Silverman LB, Couban S, Supko JG, et al. Long-term outcome of a pediatric-inspired regimen used for adults aged 18–50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia. 2015;29:526–34. Available from: CrossRefPubMedGoogle Scholar
  46. 46.
    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. Available from: CrossRefPubMedGoogle Scholar
  47. 47.
    Yanada M, Jinnai I, Takeuchi J, Ueda T, Miyawaki S, Tsuzuki M, et al. Clinical features and outcome of T-lineage acute lymphoblastic leukemia in adults: a low initial white blood cell count, as well as a high count predict decreased survival rates. Leuk Res. 2007;31:907–14. Available from: CrossRefPubMedGoogle Scholar
  48. 48.
    Asselin BL, Devidas M, Wang C, Pullen J, Borowitz MJ, Hutchison R, et al. Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children’s oncology group (POG 9404). Blood. 2011;118:874–83. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    • Sancho J-M, Ribera J-M, Oriol A, Hernandez-Rivas J-M, Rivas C, Bethencourt C, et al. Central nervous system recurrence in adult patients with acute lymphoblastic leukemia: frequency and prognosis in 467 patients without cranial irradiation for prophylaxis. Cancer. 2006;106:2540–6. Available from: The impact of prophylactic CNS irradiation in addition to intratechal chemotherapy on outcomes in pediatric T-ALL. CrossRefPubMedGoogle Scholar
  50. 50.
    Kantarjian HM, O’Brien S, Smith TL, Cortes J, Giles FJ, Beran M, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000;18:547–61. Available from: CrossRefPubMedGoogle Scholar
  51. 51.
    Cahu X, Labopin M, Giebel S, Socie G, Beelen D, Arnold R, et al. Myeloablative allogeneic hematopoietic stem cell transplantation for adult patients with T-cell acute lymphoblastic leukemia: a survey from the acute leukemia working Party of the European Group for blood and marrow transplantation (EBMT). Blood. 2012;120:356.CrossRefGoogle Scholar
  52. 52.
    Cahu X, Labopin M, Giebel S, Aljurf M, Kyrcz-Krzemien S, Socié G, et al. Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT. Bone Marrow Transplant. 2016;51:351–7. Available from: CrossRefPubMedGoogle Scholar
  53. 53.
    Roth-Guepin G, Canaani J, Ruggeri A, Labopin M, Finke J, Cornelissen JJ, et al. Allogeneic stem cell transplantation in acute lymphoblastic leukemia patients older than 60 years: a survey from the acute leukemia working party of EBMT. Oncotarget. 2017;8:112972–9. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Marks DI, Wang T, Pérez WS, Antin JH, Copelan E, Gale RP, et al. The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission. Blood. 2010;116:366–74. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Guièze R, Cornillet-Lefebvre P, Lioure B, Blanchet O, Pigneux A, Recher C, et al. Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3-ITD molecular status for cytogenetically normal AML patients: a GOELAMS study. Am J Hematol. 2012;87:1052–6. [cited 2013 Sep 8]. Available from: CrossRefPubMedGoogle Scholar
  56. 56.
    Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007;109:944–50. Available from: CrossRefPubMedGoogle Scholar
  57. 57.
    Hijiya N, Thomson B, Isakoff MS, Silverman LB, Steinherz PG, Borowitz MJ, et al. Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. Blood. 2011;118:6043–9. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Raetz EA, Borowitz MJ, Devidas M, Linda SB, Hunger SP, Winick NJ, et al. Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: A Children’s Oncology Group Study[corrected]. J Clin Oncol. 2008;26:3971–8. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Specchia G, Pastore D, Carluccio P, Liso A, Mestice A, Rizzi R, et al. FLAG-IDA in the treatment of refractory/relapsed adult acute lymphoblastic leukemia. Ann Hematol. 2005;84:792–5. Available from: CrossRefPubMedGoogle Scholar
  60. 60.
    Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, et al. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children’s Oncology Group. J Clin Oncol. 2005;23:3376–82. Available from: CrossRefPubMedGoogle Scholar
  61. 61.
    Gökbuget N, Basara N, Baurmann H, Beck J, Brüggemann M, Diedrich H, et al. High single-drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation. Blood. 2011;118:3504–11. Available from: CrossRefPubMedGoogle Scholar
  62. 62.
    DeAngelo DJ, Yu D, Johnson JL, Coutre SE, Stone RM, Stopeck AT, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and leukemia group B study 19801. Blood. 2007;109:5136–42. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Dunsmore KP, Devidas M, Linda SB, Borowitz MJ, Winick N, Hunger SP, et al. Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia: a report from the Children’s Oncology Group. J Clin Oncol. 2012;30:2753–9. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Abaza YM, Kantarjian H, Faderl S, Jabbour E, Jain N, Thomas D, et al. Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma. Am J Hematol. 2018;93:91–9.CrossRefPubMedGoogle Scholar
  65. 65.
    Farhadfar N, Litzow MR. New monoclonal antibodies for the treatment of acute lymphoblastic leukemia. Leuk Res . Elsevier Ltd. 2016;49:13–21. Scholar
  66. 66.
    Hernandez Tejada FN, Galvez Silva JR, Zweidler-McKay PA. The challenge of targeting notch in hematologic malignancies. Front Pediatr. 2014;2:54. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Tasian SK, Teachey DT, Rheingold SR. Targeting the PI3K/mTOR pathway in pediatric hematologic malignancies. Front Oncol. 2014;4:108. Available from: PubMedPubMedCentralGoogle Scholar
  68. 68.
    Dorritie KA, McCubrey JA, Johnson DE. STAT transcription factors in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention. Leukemia. 2014;28:248–57. Available from: CrossRefPubMedGoogle Scholar
  69. 69.
    Aleem E, Arceci RJ. Targeting cell cycle regulators in hematologic malignancies. Front Cell Dev Biol. 2015;3:16. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Irving JAE. Towards an understanding of the biology and targeted treatment of paediatric relapsed acute lymphoblastic leukaemia. Br J Haematol. 2016;172:655–66. Available from: CrossRefPubMedGoogle Scholar
  71. 71.
    Niewerth D, Dingjan I, Cloos J, Jansen G, Kaspers G. Proteasome inhibitors in acute leukemia. Expert Rev Anticancer Ther. 2013;13:327–37. Available from: CrossRefPubMedGoogle Scholar
  72. 72.
    Peirs S, Van der Meulen J, Van de Walle I, Taghon T, Speleman F, Poppe B, et al. Epigenetics in T-cell acute lymphoblastic leukemia. Immunol Rev. 2015;263:50–67. Available from: CrossRefPubMedGoogle Scholar
  73. 73.
    Durinck K, Goossens S, Peirs S, Wallaert A, Van Loocke W, Matthijssens F, et al. Novel biological insights in T-cell acute lymphoblastic leukemia. Exp Hematol. 2015;43:625–39. Scholar
  74. 74.
    Deangelo DJ, Stone RM, Silverman LB, Stock W, Attar EC, Fearen I, et al. A phase I clinical trial of the notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and other leukemias [abstract]. J Clin Oncol. 2006;24:6585.Google Scholar
  75. 75.
    Real PJ, Tosello V, Palomero T, Castillo M, Hernando E, de Stanchina E, et al. Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nat Med. 2009;15:50–8. Available from: CrossRefPubMedGoogle Scholar
  76. 76.
    Zweidler-McKay PA, DeAngelo DJ, Douer D, Dombret H, Ottmann OG, Vey N, et al. The safety and activity of BMS-906024, a gamma secretase inhibitor (GSI) with anti-notch activity, in patients with relapsed T-cell acute lymphoblastic leukemia (T-ALL): initial results of a phase 1 trial [abstract]. Blood. 2014;124:968.Google Scholar
  77. 77.
    Wu Y, Cain-Hom C, Choy L, Hagenbeek TJ, de Leon GP, Chen Y, et al. Therapeutic antibody targeting of individual notch receptors. Nature. 2010;464:1052–7. Available from: CrossRefPubMedGoogle Scholar
  78. 78.
    Moellering RE, Cornejo M, Davis TN, Del Bianco C, Aster JC, Blacklow SC, et al. Direct inhibition of the NOTCH transcription factor complex. Nature. 2009;462:182–8. Available from: CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of HematologyMayo ClinicRochesterUSA

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