Frontiers of Medicine

, Volume 6, Issue 4, pp 416–420 | Cite as

Early T-cell precursor leukemia: a subtype of high risk childhood acute lymphoblastic leukemia

  • Meilin Ma
  • Xiang Wang
  • Jingyan Tang
  • Huiliang Xue
  • Jing Chen
  • Ci Pan
  • Hua Jiang
  • Shuhong ShenEmail author
Research Article


Acute lymphoblastic leukemia includes T-cell acute lymphoblastic leukemia (T-ALL) and B-cell acute lymphoblastic leukemia (B-ALL). In children, T-ALL usually has a worse prognosis than B-ALL, although childhood T-ALL prognoses have improved remarkably. The varying outcomes among T-ALL cases suggest that an unrecognized biological heterogeneity may contribute to chemo-resistance. Deep exploration of T-lymphocyte development in recent years has found a subgroup of patients with a phenotype that resembles early T-cell precursor, which confers a much poorer prognosis than any other form of T-ALL. This novel subtype of T-ALL was called early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Flow cytometry data from T-ALL patients enrolled in Shanghai Children’s Medical Center between July 2002 and October 2010 were assessed according to Dr. Campana’s protocol. Among total 89 T-ALL cases, 74 cases had enough immunophenotype data available to differentiate between ETP (CD1a, CD8, CD5dim, at least one marker of stem cell or myeloid lineage) and non-ETP. From these 74 subjects, 12 ETP-ALL cases (16.2%) were identified. The event-free survival (EFS) rate at 66.8 months was 11.1% ± 10.1% for ETP-ALL and 57.6% ± 5.6% for non-ETP-ALL (P = 0.003). The overall survival rates were 13.3% ± 11.0% for ETP-ALL and 64.7% ± 6.3% for non-ETP-ALL (P = 0.002). Our findings demonstrate that early T-cell precursor leukemia is a very high-risk subtype of acute lymphoblastic leukemia with poor prognosis.


acute lymphoblastic leukemia early T precursor prognosis 


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  1. 1.
    Zhang RD, Liu Y, Zhang YH, Xie J, Jiang J, Wang B, Zheng HY, Li ZG, Wu MY. Clinical significance of minimal residual disease in monitoring relapse of childhood acute T-cell lymphoblastic leukemia. J China Pediatr Blood Cancer (Zhongguo Xiao Er Xue Ye Yu Zhong Liu Za Zhi) 2011; 16: 203–206 (in Chinese)Google Scholar
  2. 2.
    Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006; 354(2): 166–178PubMedCrossRefGoogle Scholar
  3. 3.
    Pullen J, Shuster JJ, Link M, Borowitz M, Amylon M, Carroll AJ, Land V, Look AT, McIntyre B, Camitta B. Significance of commonly used prognostic factors differs for children with T cell acute lymphocytic leukemia (ALL), as compared to those with Bprecursor ALL. A Pediatric Oncology Group (POG) study. Leukemia 1999; 13(11): 1696–1707PubMedCrossRefGoogle Scholar
  4. 4.
    Pui CH, Hancock ML, Head DR, Rivera GK, Look AT, Sandlund JT, Behm FG. Clinical significance of CD34 expression in childhood acute lymphoblastic leukemia. Blood 1993; 82(3): 889–894PubMedGoogle Scholar
  5. 5.
    Pui CH, Rivera GK, Hancock ML, Raimondi SC, Sandlund JT, Mahmoud HH, Ribeiro RC, Furman WL, Hurwitz CA, Crist WM, et al. Clinical significance of CD10 expression in childhood acute lymphoblastic leukemia. Leukemia 1993; 7(1): 35–40PubMedGoogle Scholar
  6. 6.
    Thiel E, Kranz BR, Raghavachar A, Bartram CR, Löffler H, Messerer D, Ganser A, Ludwig WD, Büchner T, Hoelzer D. Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia. Blood 1989; 73(5): 1247–1258PubMedGoogle Scholar
  7. 7.
    Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, Behm FG, Pui CH, Downing JR, Gilliland DG, Lander ES, Golub TR, Look AT. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 2002; 1(1): 75–87PubMedCrossRefGoogle Scholar
  8. 8.
    Ferrando AA, Neuberg DS, Dodge RK, Paietta E, Larson RA, Wiernik PH, Rowe JM, Caligiuri MA, Bloomfield CD, Look AT. Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Lancet 2004; 363(9408): 535–536PubMedCrossRefGoogle Scholar
  9. 9.
    Cavé H, Suciu S, Preudhomme C, Poppe B, Robert A, Uyttebroeck A, Malet M, Boutard P, Benoit Y, Mauvieux L, Lutz P, Méchinaud F, Grardel N, Mazingue F, Dupont M, Margueritte G, Pages MP, Bertrand Y, Plouvier E, Brunie G, Bastard C, Plantaz D, Vande Velde I, Hagemeijer A, Speleman F, Lessard M, Otten J, Vilmer E, Dastugue N; EORTC-CLG. Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951. Blood 2004; 103(2): 442–450PubMedCrossRefGoogle Scholar
  10. 10.
    Breit S, Stanulla M, Flohr T, Schrappe M, Ludwig WD, Tolle G, Happich M, Muckenthaler MU, Kulozik AE. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood 2006; 108(4): 1151–1157PubMedCrossRefGoogle Scholar
  11. 11.
    Rothenberg EV, Moore JE, Yui MA. Launching the T-cell-lineage developmental programme. Nat Rev Immunol 2008; 8(1): 9–21PubMedCrossRefGoogle Scholar
  12. 12.
    Bell JJ, Bhandoola A. The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature 2008; 452(7188): 764–767PubMedCrossRefGoogle Scholar
  13. 13.
    Wada H, Masuda K, Satoh R, Kakugawa K, Ikawa T, Katsura Y, Kawamoto H. Adult T-cell progenitors retain myeloid potential. Nature 2008; 452(7188): 768–772PubMedCrossRefGoogle Scholar
  14. 14.
    Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, Cheng C, Su X, Rubnitz JE, Basso G, Biondi A, Pui CH, Downing JR, Campana D. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 2009; 10(2): 147–156PubMedCrossRefGoogle Scholar
  15. 15.
    Wang YR, Jin RM, Xu JW, Xiao Y, Zhou DF, Zhang ZQ. Therapeutic effectiveness of the ALL-XH-99 protocol for childhood acute lymphoblastic leukemia. Chin J Contemp Pediatr (Zhongguo Dang Dai Er Ke Za Zhi ) 2008; 10(1): 1–4 (in Chinese)Google Scholar
  16. 16.
    Zhu YP. Treatment and prognosis of acute lymphoblastic leukemia in chlidren. J Appl clin Pediatr (Shi Yong Er Ke Lin Chuang Za Zhi) 2007, 22(15): 1128–1131 (in Chinese)Google Scholar
  17. 17.
    Shuster JJ, Falletta JM, Pullen DJ, Crist WM, Humphrey GB, Dowell BL, Wharam MD, Borowitz M. Prognostic factors in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood 1990; 75(1): 166–173PubMedGoogle Scholar
  18. 18.
    Uckun FM, Gaynon PS, Sensel MG, Nachman J, Trigg ME, Steinherz PG, Hutchinson R, Bostrom BC, Sather HN, Reaman GH. Clinical features and treatment outcome of childhood T-lineage acute lymphoblastic leukemia according to the apparent maturational stage of T-lineage leukemic blasts: a Children’s Cancer Group study. J Clin Oncol 1997; 15(6): 2214–2221PubMedGoogle Scholar
  19. 19.
    Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 2012; 481(7380): 157–163PubMedCrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Meilin Ma
    • 1
  • Xiang Wang
    • 1
  • Jingyan Tang
    • 1
  • Huiliang Xue
    • 1
  • Jing Chen
    • 1
  • Ci Pan
    • 1
  • Hua Jiang
    • 1
  • Shuhong Shen
    • 1
    Email author
  1. 1.Department of Hematology/Oncology, Shanghai Children’s Medical CenterShanghai Jiaotong University School of MedicineShanghaiChina

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