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Recent Developments in the Management of T-Cell Precursor Acute Lymphoblastic Leukemia/Lymphoma

  • Acute Lymphocytic Leukemia (F Ravandi, Section Editor)
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Abstract

T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma are uncommon disorders classified together by the World Health Organization classification as “T-lymphoblastic leukemia/lymphoma.” This review gives an overview on the treatment of these aggressive but curable T cell malignancies in adult patients, in order to highlight current developments. The most interesting and relevant developments are in our understanding of the genetics of T-ALL/LBL and how the genetics relate to clinical outcome. These studies will inform clinicians as to which targeted novel agents may be of value and how patients may be best risk-stratified to receive them.

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References

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

  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(1):34–43.

    Article  PubMed  CAS  Google Scholar 

  2. Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood. 2006;107(1):265–76.

    Article  PubMed  CAS  Google Scholar 

  3. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019–32.

    Article  PubMed  CAS  Google Scholar 

  4. •• Feng H, Stachura DL, White RM, et al. T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell. 2010;18(4):353–66. An important paper examining the genetic basis for the difference between T-LBL and T-ALL. That AKT activation was identified as being important in controlling extravasation of T lymphoblasts suggests that PI3K-AKT inhibitors could be useful therapeutically, in preventing T-LBL cells from acquiring the ability to invade and disseminate.

    Article  PubMed  CAS  Google Scholar 

  5. Schatz DG, Oettinger MA, Schlissel MS. V(D)J recombination: molecular biology and regulation. Annu Rev Immunol. 1992;10:359–83.

    Article  PubMed  CAS  Google Scholar 

  6. Takahama Y. Journey through the thymus: stromal guides for T-cell development and selection. Nat Rev Immunol. 2006;6(2):127–35.

    Article  PubMed  CAS  Google Scholar 

  7. Rothenberg EV, Taghon T. Molecular genetics of T cell development. Annu Rev Immunol. 2005;23:601–49.

    Article  PubMed  CAS  Google Scholar 

  8. Asnafi V, Beldjord K, Boulanger E, 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(7):2693–703.

    Article  PubMed  CAS  Google Scholar 

  9. Bene MC. Pro-T ALL: immunophenotypical analyses. J Biol Regul Homeost Agents. 2004;18(3–4):327–30.

    PubMed  CAS  Google Scholar 

  10. Asnafi V, Beldjord K, Libura M, et al. Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy. Blood. 2004;104(13):4173–80.

    Article  PubMed  CAS  Google Scholar 

  11. Vitale A, Guarini A, Ariola C, 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(2):473–9.

    Article  PubMed  CAS  Google Scholar 

  12. • Meijerink JP. Genetic rearrangements in relation to immunophenotype and outcome in T-cell acute lymphoblastic leukaemia. Best Pract Res Clin Haematol. 2010;23(3):307–18. A very clear and concise summary of the genetics of T ALL/LBL by an expert in the field.

    Article  PubMed  CAS  Google Scholar 

  13. Garand R, Voisin S, Papin S, et al. Characteristics of pro-T ALL subgroups: comparison with late T-ALL. The Groupe d’Etude Immunologique des Leucemies. Leukemia. 1993;7(2):161–7.

    PubMed  CAS  Google Scholar 

  14. Asnafi V, Buzyn A, Thomas X, et al. Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: a LALA-94 study. Blood. 2005;105(8):3072–8.

    Article  PubMed  CAS  Google Scholar 

  15. •• Marks DI, Paietta EM, Moorman AV, 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(25):5136–45. The largest and pivotal study of patients with T-ALL—includes information on genetics, prognostic factors, and outcomes after treatment with both chemotherapy and stem cell transplants.

    Article  PubMed  CAS  Google Scholar 

  16. Fischer L, Gokbuget N, Schwartz S, et al. CD56 expression in T-cell acute lymphoblastic leukemia is associated with non-thymic phenotype and resistance to induction therapy but no inferior survival after risk-adapted therapy. Haematologica. 2009;94(2):224–9.

    Article  PubMed  CAS  Google Scholar 

  17. •• Coustan-Smith E, Mullighan CG, Onciu M, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10(2):147–56. Describes the entity of ETP-ALL for the first time. Demonstrates the extremely poor prognosis, and makes clear that the early recognition of this entity is important in order to allow consideration of early therapeutic intensification.

    Article  PubMed  CAS  Google Scholar 

  18. •• Zhang J, Ding L, Holmfeldt L, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012;481(7380):157–63. An insightful paper, examining the genetics of ETP-ALL by transcriptional profiling. Concludes that the transcriptional profile of ETP-ALL is similar to that of normal and myeloid leukemia hematopoietic stem cells suggesting that a change in therapeutic direction to therapy more commonly used for myeloid malignancies may benefit these patients.

    Article  PubMed  CAS  Google Scholar 

  19. Bergeron J, Clappier E, Radford I, et al. Prognostic and oncogenic relevance of TLX1/HOX11 expression level in T-ALLs. Blood. 2007;110(7):2324–30.

    Article  PubMed  CAS  Google Scholar 

  20. Ferrando AA, Neuberg DS, Dodge RK, et al. Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Lancet. 2004;363(9408):535–6.

    Article  PubMed  CAS  Google Scholar 

  21. Baak U, Gokbuget N, Orawa H, 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(6):1154–60.

    Article  PubMed  CAS  Google Scholar 

  22. Krieger D, Moericke A, Oschlies I, et al. Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia. Haematologica. 2010;95(1):158–62.

    Article  PubMed  CAS  Google Scholar 

  23. Weng AP, Ferrando AA, Lee W, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306(5694):269–71.

    Article  PubMed  CAS  Google Scholar 

  24. O’Neil J, Grim J, Strack P, et al. FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med. 2007;204(8):1813–24.

    Article  PubMed  Google Scholar 

  25. Buonamici S, Trimarchi T, Ruocco MG, et al. CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia. Nature. 2009;459(7249):1000–4.

    Article  PubMed  CAS  Google Scholar 

  26. • Asnafi V, Buzyn A, Le Noir S, 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(17):3918–24. Identifies a large group of patients with NOTCH1 or FBXW7 mutations who have a good outcome. Goes some way to explaining that could be why adult patients with T-ALL have relatively good outcomes.

    Article  PubMed  CAS  Google Scholar 

  27. Baldus CD, Thibaut J, Goekbuget N, et al. Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia. Haematologica. 2009;94(10):1383–90.

    Article  PubMed  CAS  Google Scholar 

  28. Mansour MR, Sulis ML, Duke V, et al. Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol. J Clin Oncol. 2009;27(26):4352–6.

    Article  PubMed  CAS  Google Scholar 

  29. Reiter A, Schrappe M, Ludwig WD, et al. Intensive ALL-type therapy without local radiotherapy provides a 90 % event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. Blood. 2000;95(2):416–21.

    PubMed  CAS  Google Scholar 

  30. Thomas DA, O’Brien S, Cortes J, et al. Outcome with the hyper-CVAD regimens in lymphoblastic lymphoma. Blood. 2004;104(6):1624–30.

    Article  PubMed  CAS  Google Scholar 

  31. Cairo MS, Coiffier B, Reiter A, Younes A. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149(4):578–86.

    Article  PubMed  CAS  Google Scholar 

  32. Will A, Tholouli E. The clinical management of tumour lysis syndrome in haematological malignancies. Br J Haematol. 2011;154(1):3–13.

    Article  PubMed  CAS  Google Scholar 

  33. Pui CH. Rasburicase: a potent uricolytic agent. Expert Opin Pharmacother. 2002;3(4):433–42.

    Article  PubMed  CAS  Google Scholar 

  34. Annino L, Vegna ML, Camera A, et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood. 2002;99(3):863–71.

    Article  PubMed  CAS  Google Scholar 

  35. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005;106(12):3760–7.

    Article  PubMed  CAS  Google Scholar 

  36. Larson RA, Dodge RK, Linker CA, et al. A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood. 1998;92(5):1556–64.

    PubMed  CAS  Google Scholar 

  37. Kantarjian H, Thomas D, O’Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101(12):2788–801.

    Article  PubMed  CAS  Google Scholar 

  38. Gokbuget N, Hoelzer D, Arnold R, et al. Treatment of adult ALL according to protocols of the German Multicenter Study Group for Adult ALL (GMALL). Hematol Oncol Clin North Am. 2000;14(6):1307–25. ix.

    Article  PubMed  CAS  Google Scholar 

  39. Fiere D, Lepage E, Sebban C, et al. Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. The French group on therapy for adult acute lymphoblastic leukemia. J Clin Oncol. 1993;11(10):1990–2001.

    PubMed  CAS  Google Scholar 

  40. Patel B, Rai L, Buck G, et al. Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993. Br J Haematol. 2010;148(1):80–9.

    Article  PubMed  CAS  Google Scholar 

  41. Mortuza FY, Papaioannou M, Moreira IM, et al. Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia. J Clin Oncol. 2002;20(4):1094–104.

    Article  PubMed  Google Scholar 

  42. Bruggemann M, Raff T, Flohr T, et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006;107(3):1116–23.

    Article  PubMed  Google Scholar 

  43. Bruggemann M, Schrauder A, Raff T, et al. Standardized MRD quantification in European ALL trials: proceedings of the second international symposium on MRD assessment in Kiel, Germany, 18–20 September 2008. Leukemia. 2010;24(3):521–35.

    Article  PubMed  CAS  Google Scholar 

  44. Robillard N, Cave H, Mechinaud F, et al. Four-color flow cytometry bypasses limitations of IG/TCR polymerase chain reaction for minimal residual disease detection in certain subsets of children with acute lymphoblastic leukemia. Haematologica. 2005;90(11):1516–23.

    PubMed  CAS  Google Scholar 

  45. Coustan-Smith E, Song G, Clark C, et al. New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2011;117(23):6267–76.

    Article  PubMed  CAS  Google Scholar 

  46. Krampera M, Vitale A, Vincenzi C, et al. Outcome prediction by immunophenotypic minimal residual disease detection in adult T-cell acute lymphoblastic leukaemia. Br J Haematol. 2003;120(1):74–9.

    Article  PubMed  Google Scholar 

  47. Bruggemann M, van der Velden VH, Raff T, et al. Rearranged T-cell receptor beta genes represent powerful targets for quantification of minimal residual disease in childhood and adult T-cell acute lymphoblastic leukemia. Leukemia. 2004;18(4):709–19.

    Article  PubMed  CAS  Google Scholar 

  48. Sullivan MP, Boyett J, Pullen J, et al. Pediatric oncology group experience with modified LSA2-L2 therapy in 107 children with non-Hodgkin’s lymphoma (Burkitt’s lymphoma excluded). Cancer. 1985;55(2):323–36.

    Article  PubMed  CAS  Google Scholar 

  49. Attarbaschi A, Mann G, Dworzak M, Wiesbauer P, Schrappe M, Gadner H. Mediastinal mass in childhood T-cell acute lymphoblastic leukemia: significance and therapy response. Med Pediatr Oncol. 2002;39(6):558–65.

    Article  PubMed  Google Scholar 

  50. Hoelzer D, Gokbuget N, Digel W, et al. Outcome of adult patients with T-lymphoblastic lymphoma treated according to protocols for acute lymphoblastic leukemia. Blood. 2002;99(12):4379–85.

    Article  PubMed  CAS  Google Scholar 

  51. Cheson BD. Role of functional imaging in the management of lymphoma. J Clin Oncol. 2011;29(14):1844–54.

    Article  PubMed  Google Scholar 

  52. Feeney J, Horwitz S, Gonen M, Schoder H. Characterization of T-cell lymphomas by FDG PET/CT. AJR Am J Roentgenol. 2010;195(2):333–40.

    Article  PubMed  Google Scholar 

  53. • Meignan M, Gallamini A, Haioun C, Polliack A. Report on the second international workshop on interim positron emission tomography in lymphoma held in Menton, France, 8–9 April 2010. Leuk Lymphoma. 2010;51(12):2171–80. A useful pragmatic summary of expert opinion on the role of PET in managing patients with lymphoma. Important topic for clinicians trying to decide how best to use PET in managing patients with T-LBL.

    Article  PubMed  Google Scholar 

  54. Pui CH, Campana D, Pei D, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med. 2009;360(26):2730–41.

    Article  PubMed  CAS  Google Scholar 

  55. Matloub Y, Lindemulder S, Gaynon PS, et al. Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children’s Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the children’s oncology group. Blood. 2006;108(4):1165–73.

    Article  PubMed  Google Scholar 

  56. Clarke M, Gaynon P, Hann I, et al. CNS-directed therapy for childhood acute lymphoblastic leukemia: childhood ALL collaborative group overview of 43 randomized trials. J Clin Oncol. 2003;21(9):1798–809.

    Article  PubMed  CAS  Google Scholar 

  57. Kager L, Cheok M, Yang W, et al. Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics. J Clin Invest. 2005;115(1):110–7.

    PubMed  CAS  Google Scholar 

  58. Schrappe M, Reiter A, Zimmermann M, et al. Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Munster. Leukemia. 2000;14(12):2205–22.

    Article  PubMed  CAS  Google Scholar 

  59. Cortelazzo S, Intermesoli T, Oldani E, et al. Results of a lymphoblastic leukemia-like chemotherapy program with risk-adapted mediastinal irradiation and stem cell transplantation for adult patients with lymphoblastic lymphoma. Ann Hematol. 2012;91(1):73–82.

    Article  PubMed  CAS  Google Scholar 

  60. Goldstone AH, Richards SM, Lazarus HM, 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(4):1827–33.

    Article  PubMed  CAS  Google Scholar 

  61. Milpied N, Ifrah N, Kuentz M, et al. Bone marrow transplantation for adult poor prognosis lymphoblastic lymphoma in first complete remission. Br J Haematol. 1989;73(1):82–7.

    Article  PubMed  CAS  Google Scholar 

  62. Santini G, Coser P, Chisesi T, et al. Autologous bone marrow transplantation for advanced stage adult lymphoblastic lymphoma in first complete remission. Report of the Non-Hodgkin’s Lymphoma Cooperative Study Group (NHLCSG). Ann Oncol. 1991;2 Suppl 2:181–5.

    PubMed  Google Scholar 

  63. Verdonck LF, Dekker AW, de Gast GC, Lokhorst HM, Nieuwenhuis HK. Autologous bone marrow transplantation for adult poor-risk lymphoblastic lymphoma in first remission. J Clin Oncol. 1992;10(4):644–6.

    PubMed  CAS  Google Scholar 

  64. Sweetenham JW, Liberti G, Pearce R, Taghipour G, Santini G, Goldstone AH. High-dose therapy and autologous bone marrow transplantation for adult patients with lymphoblastic lymphoma: results of the European group for bone marrow transplantation. J Clin Oncol. 1994;12(7):1358–65.

    PubMed  CAS  Google Scholar 

  65. Sweetenham JW, Santini G, Qian W, et al. High-dose therapy and autologous stem-cell transplantation versus conventional-dose consolidation/maintenance therapy as postremission therapy for adult patients with lymphoblastic lymphoma: results of a randomized trial of the European group for blood and marrow transplantation and the United Kingdom lymphoma group. J Clin Oncol. 2001;19(11):2927–36.

    PubMed  CAS  Google Scholar 

  66. Hunault M, Truchan-Graczyk M, Caillot D, et al. Outcome of adult T-lymphoblastic lymphoma after acute lymphoblastic leukemia-type treatment: a GOELAMS trial. Haematologica. 2007;92(12):1623–30.

    Article  PubMed  CAS  Google Scholar 

  67. Rodriguez Jr CO, Gandhi V. Arabinosylguanine-induced apoptosis of T-lymphoblastic cells: incorporation into DNA is a necessary step. Cancer Res. 1999;59(19):4937–43.

    PubMed  CAS  Google Scholar 

  68. Kurtzberg J, Ernst TJ, Keating MJ, et al. Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies. J Clin Oncol. 2005;23(15):3396–403.

    Article  PubMed  CAS  Google Scholar 

  69. DeAngelo DJ, Yu D, Johnson JL, 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(12):5136–42.

    Article  PubMed  CAS  Google Scholar 

  70. Czuczman MS, Porcu P, Johnson J, et al. Results of a phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901. Leuk Lymphoma. 2007;48(1):97–103.

    Article  PubMed  CAS  Google Scholar 

  71. •• Gokbuget N, Basara N, Baurmann 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(13):3504–11. Largest study of patients with relapsed T-ALL/LBL. Demonstrates an important role for nelarabine in this patient population. Indicates why nelarabine is being studied “up front” in patients with newly diagnosed T-ALL by two major national ALL study groups.

    Article  PubMed  Google Scholar 

  72. Parker WB, Shaddix SC, Chang CH, et al. Effects of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine on K562 cellular metabolism and the inhibition of human ribonucleotide reductase and DNA polymerases by its 5′-triphosphate. Cancer Res. 1991;51(9):2386–94.

    PubMed  CAS  Google Scholar 

  73. Karp JE, Ricklis RM, Balakrishnan K, et al. A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias. Blood. 2007;110(6):1762–9.

    Article  PubMed  CAS  Google Scholar 

  74. Kantarjian H, Gandhi V, Cortes J, et al. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003;102(7):2379–86.

    Article  PubMed  CAS  Google Scholar 

  75. Kicska GA, Long L, Horig H, et al. Immucillin H, a powerful transition-state analog inhibitor of purine nucleoside phosphorylase, selectively inhibits human T lymphocytes. Proc Natl Acad Sci U S A. 2001;98(8):4593–8.

    Article  PubMed  CAS  Google Scholar 

  76. Homminga I, Zwaan CM, Manz CY, et al. In vitro efficacy of forodesine and nelarabine (ara-G) in pediatric leukemia. Blood. 2011;118(8):2184–90.

    Article  PubMed  CAS  Google Scholar 

  77. Gandhi V, Kilpatrick JM, Plunkett W, et al. A proof-of-principle pharmacokinetic, pharmacodynamic, and clinical study with purine nucleoside phosphorylase inhibitor immucillin-H (BCX-1777, forodesine). Blood. 2005;106(13):4253–60.

    Article  PubMed  CAS  Google Scholar 

  78. Palomero T, Dominguez M, Ferrando AA. The role of the PTEN/AKT Pathway in NOTCH1-induced leukemia. Cell Cycle. 2008;7(8):965–70.

    Article  PubMed  CAS  Google Scholar 

  79. Palomero T, Sulis ML, Cortina M, et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med. 2007;13(10):1203–10.

    Article  PubMed  CAS  Google Scholar 

  80. Okuhashi Y, Itoh M, Nara N, Tohda S. Effects of combination of notch inhibitor plus hedgehog inhibitor or Wnt inhibitor on growth of leukemia cells. Anticancer Res. 2011;31(3):893–6.

    PubMed  CAS  Google Scholar 

  81. Rao SS, O’Neil J, Liberator CD, et al. Inhibition of NOTCH signaling by gamma secretase inhibitor engages the RB pathway and elicits cell cycle exit in T-cell acute lymphoblastic leukemia cells. Cancer Res. 2009;69(7):3060–8.

    Article  PubMed  CAS  Google Scholar 

  82. Real PJ, Tosello V, Palomero T, et al. Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nat Med. 2009;15(1):50–8.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, University College London, Royal Free Campus, Rowland Hill St, London, NW3 2PF, UK

    Adele K. Fielding & Lalita Banerjee

  2. Hematology and Oncology Center, University Hospitals Bristol, Horfield Road, Bristol, BS2 8ED, UK

    David I. Marks

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  1. Adele K. Fielding
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  2. Lalita Banerjee
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Correspondence to Adele K. Fielding.

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Fielding, A.K., Banerjee, L. & Marks, D.I. Recent Developments in the Management of T-Cell Precursor Acute Lymphoblastic Leukemia/Lymphoma. Curr Hematol Malig Rep 7, 160–169 (2012). https://doi.org/10.1007/s11899-012-0123-4

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