Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia

被引:692
作者
Coustan-Smith, Elaine [1 ]
Mullighan, Charles G. [2 ]
Onciu, Mihaela [2 ]
Behm, Frederick G. [2 ]
Raimondi, Susana C. [2 ,4 ]
Pei, Deqing [3 ]
Cheng, Cheng [3 ]
Su, Xiaoping [2 ]
Rubnitz, Jeffrey E. [1 ,4 ]
Basso, Giuseppe [5 ]
Biondi, Andrea [6 ]
Pui, Ching-Hon [1 ,2 ,4 ]
Downing, James R. [2 ,4 ]
Campana, Dario [1 ,2 ,4 ]
机构
[1] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA
[2] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA
[3] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA
[4] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA
[5] Univ Padua, Dept Pediat, Padua, Italy
[6] Univ Milan, Dept Pediat, M Tettamanti Res Ctr, Monza, Italy
关键词
MINIMAL RESIDUAL DISEASE; CLINICAL-SIGNIFICANCE; PROGNOSTIC-FACTORS; EXPRESSION; CHILDREN; PROGENITORS; THERAPY; MUTATIONS; DIAGNOSIS; PREDICTS;
D O I
10.1016/S1470-2045(08)70314-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background About a fifth of children with acute T-lymphoblastic leukaemia (T-ALL) succumb to the disease, suggesting an unrecognised biological heterogeneity that might contribute to drug resistance. We postulated that T-ALL originating from early T-cell precursors (ETPs), a recently defined subset of thymocytes that retain stem-cell-like features, would respond poorly to lymphoid-cell-directed therapy. We studied leukaemic cells, collected at diagnosis, to identify cases with ETP features and determine their clinical outcome. Methods Leukaemic cells from 239 patients with T-ALL enrolled at St Jude Children's Research Hospital (n=139) and in the Italian national study Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) ALL-2000 (n=100) were assessed by gene-expression profiling, flow cytometry, and single nucleotide polymorphism array analysis. Probabilities of survival and treatment failure were calculated for subgroups considered to have ETP-ALL or typical T-ALL. Findings 30 patients (12.6%) had leukaemic lymphoblasts with an ETP-related gene-expression signature or its associated distinctive immunophenotype (CD1a(-), CD8(-), CD5(weak) with stem-cell or myeloid markers). Cases of ETP-ALL showed increased genomic instability, in terms of number and size of gene lesions, compared with those with typical T-ALL. Patients with this form of leukaemia had high risk of remission failure or haematological relapse (72% [95% CI 40-100] at 10 years vs 10% [4-16] at 10 years for patients with typical T-ALL treated at St Jude Children's Research Hospital; and 57% [25-89] at 2 years vs 14% [6-22] at 2 years for patients treated in the AIEOP trial). Interpretation ETP-ALL is a distinct, previously unrecognised, pathobiological entity that confers a poor prognosis with use of standard intensive chemotherapy. Its early recognition, by use of the gene expression and immunophenotypic criteria outlined here, is essential for the development of an effective clinical management strategy.
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收藏
页码:147 / 156
页数:10
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