Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia.
Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia.
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DOI：
10.1016/s1470-2045(08)70314-0
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发表时间：
2009-02
期刊：
影响因子：
51.1
通讯作者：
Campana, Dario
中科院分区：
文献类型：
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作者：
Coustan-Smith, Elaine;Mullighan, Charles G.;Onciu, Mihaela;Behm, Frederick G.;Raimondi, Susana C.;Pei, Deqing;Cheng, Cheng;Su, Xiaoping;Rubnitz, Jeffrey E.;Basso, Giuseppe;Biondi, Andrea;Pui, Ching-Hon;Downing, James R.;Campana, Dario
大约五分之一的急性t淋巴细胞白血病（T-ALL）患儿死于该疾病，这表明未被识别的生物学异质性可能导致耐药性。我们假设起源于早期t细胞前体（ETPs）的T-ALL对淋巴细胞定向治疗反应不佳，ETPs是一种最近定义的胸腺细胞亚群，保留了干细胞样特征。我们研究了诊断时收集的白血病细胞，以确定具有ETP特征的病例并确定其临床结果。来自圣犹达医院和意大利国家研究AIEOP ALL-2000的239例T-ALL患者的白血病细胞通过基因表达谱、流式细胞术和单核苷酸多态性阵列分析进行了检测。计算ETP-ALL或典型T-ALL亚组的生存和治疗失败概率。30例患者（12.6%）白血病淋巴母细胞具有etp相关基因表达特征或其相关的独特免疫表型（CD1a−,CD8−，cd5弱与干细胞/髓系标志物）。ETP-ALL病例显示基因组不稳定性增加。这种形式的白血病患者缓解失败或血液学复发的比例非常高：10年时为72%(95%可信区间，40%至100%)，而在St. Jude治疗的典型TALL患者为10%(4%至16%)；2年时57%(25% - 89%)，而AIEOP试验患者为14%（6% - 22%）。ETP-ALL是一种独特的、以前未被认识到的病理实体，使用标准强化化疗会带来可怕的预后。它的早期识别，使用这里概述的标准，对制定有效的临床管理策略至关重要。
Approximately one-fifth of children with acute T-lymphoblastic leukemia (T-ALL) succumb to the disease, suggesting unrecognized biologic heterogeneity that may contribute to drug resistance. We hypothesized 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 leukemic cells, collected at diagnosis, to identify cases with ETP features and determine their clinical outcome. Leukemic cells from 239 patients with T-ALL enrolled at St. Jude and in the Italian national study AIEOP ALL-2000 were examined 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. Thirty patients (12.6%) had leukemic lymphoblasts with an ETP-related gene expression signature or its associated distinctive immunophenotype (CD1a−, CD8−, CD5weak with stem-cell/myeloid markers). Cases of ETP-ALL showed increased genomic instability. Patients with this form of leukemia had a very high proportion of remission failure or hematologic relapse: 72% (95% confidence interval, 40% to 100%) at 10 years versus 10% (4% to 16%) for typical TALL patients treated at St. Jude; and 57% (25% to 89%) at 2 years versus 14% (6% to 22%) for patients treated in the AIEOP trial. ETP-ALL is a distinct, previously unrecognized, pathobiologic entity that confers a dire prognosis with use of standard intensive chemotherapy. Its early recognition, using the criteria outlined here, is essential for the development of an effective clinical management strategy.