Novel biological insights in T-cell acute lymphoblastic leukemia
Novel biological insights in T-cell acute lymphoblastic leukemia
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DOI：
10.1016/j.exphem.2015.05.017
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发表时间：
2015-08-01
影响因子：
2.6
通讯作者：
Van Vlierberghe, Pieter
中科院分区：
文献类型：
--
作者：
Durinck, Kaat;Goossens, Steven;Van Vlierberghe, Pieter
T 细胞急性淋巴细胞白血病 (T-ALL) 是一种侵袭性血癌，约占儿童急性淋巴细胞白血病 (ALL) 病例的 15% 和成人急性淋巴细胞白血病 (ALL) 病例的 25%。它被认为是癌症发生和进展的多步骤性质的范例。遗传和表观遗传重编程事件将 T 细胞前体转化为恶性 T-ALL 淋巴母细胞，在过去十年中已得到广泛表征。尽管我们对人类 T-ALL 的基因组图谱有了全面的了解，但白血病患者仍然接受高剂量多药化疗，随后可能进行造血干细胞移植。即使采用这种通常与相当大的急性和长期副作用相关的积极治疗方案，由于获得性治疗耐药性，约 15% 的儿童和 40% 的成人 T-ALL 患者仍然会复发，并且生存前景非常黯淡。不幸的是，残留的 T-ALL 肿瘤细胞在化疗中存活并作为白血病进展和血液学复发的储存库的分子机制仍然知之甚少。尽管如此，预计增强对 T-ALL 疾病生物学的分子理解将最终促进靶向治疗驱动的方法，通过个性化挽救治疗减少化疗相关毒性并提高难治性 T-ALL 患者的生存率。在这篇综述中，我们总结了最近对 T-ALL 分子发病机制的生物学见解，并推测 T-ALL 的遗传景观如何触发人类 T-ALL 治疗新治疗策略的开发。版权所有 (C) 2015 ISEH - 国际实验血液学协会。由爱思唯尔公司出版
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer that accounts for about 15% of pediatric and 25% of adult acute lymphoblastic leukemia (ALL) cases. It is considered as a paradigm for the multistep nature of cancer initiation and progression. Genetic and epigenetic reprogramming events, which transform T-cell precursors into malignant T-ALL lymphoblasts, have been extensively characterized over the past decade. Despite our comprehensive understanding of the genomic landscape of human T-ALL, leukemia patients are still treated by high-dose multiagent chemotherapy, potentially followed by hematopoietic stem cell transplantation. Even with such aggressive treatment regimens, which are often associated with considerable acute and long-term side effects, about 15% of pediatric and 40% of adult T-ALL patients still relapse, owing to acquired therapy resistance, and present with very dismal survival perspectives. Unfortunately, the molecular mechanisms by which residual T-ALL tumor cells survive chemotherapy and act as a reservoir for leukemic progression and hematologic relapse remain poorly understood. Nevertheless, it is expected that enhanced molecular understanding of T-ALL disease biology will ultimately facilitate a targeted therapy driven approach that can reduce chemotherapy-associated toxicities and improve survival of refractory T-ALL patients through personalized salvage therapy. In this review, we summarize recent biological insights into the molecular pathogenesis of T-ALL and speculate how the genetic landscape of T-ALL could trigger the development of novel therapeutic strategies for the treatment of human T-ALL. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.