Genetic Mechanisms of Chronic Myeloid Leukemia Blastic Transformation
Genetic Mechanisms of Chronic Myeloid Leukemia Blastic Transformation
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DOI：
10.1007/s11899-012-0114-5
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发表时间：
2012-06-01
影响因子：
2.9
通讯作者：
Skorski, Tomasz
中科院分区：
文献类型：
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作者：
Skorski, Tomasz
BCR-ABL 1致癌酪氨酸激酶可转化多能造血干细胞并引发慢性期慢性髓性白血病（CML-CP），这是一种以成熟髓细胞过度积聚为特征的骨髓增生性疾病。CML-CP患者通常对ABL 1酪氨酸激酶抑制剂（TKI）（如伊马替尼）治疗有反应，尽管一些最初有反应的患者后来可能会产生耐药性。CML-CP白血病干细胞（LSC）本质上对TKI不敏感，因此可以长期存活。这些LSC或其后代可能在某些阶段获得额外的遗传变化，导致白血病从CML-CP进一步转化为更晚期的阶段，其被细分为加速期（CML-AP）或急变期（CML-BP）。CML-BP的特征是未成熟祖细胞的大规模克隆扩增，这些祖细胞具有骨髓或淋巴特征。CML-BP对治疗反应不佳，通常是致命的。本文综述了基因组不稳定性在CML急变中的作用，并提出了一些新的治疗方法。
The BCR-ABL1 oncogenic tyrosine kinase can transform pluripotent hematopoietic stem cells and initiate chronic myeloid leukemia in chronic phase (CML-CP), a myeloproliferative disorder characterized by excessive accumulation of mature myeloid cells. Patients in CML-CP usually respond to treatment with ABL1 tyrosine kinase inhibitors (TKIs) such as imatinib, though some patients who respond initially may become resistant later. CML-CP leukemia stem cells (LSCs) are intrinsically insensitive to TKIs and thus survive in the long term. These LSCs or their progeny may at some stage acquire additional genetic changes that cause the leukemia to transform further, from CML-CP to a more advanced phase, which has been subclassified as either accelerated phase (CML-AP) or blastic phase (CML-BP). CML-BP is characterized by a major clonal expansion of immature progenitors, which have either myeloid or lymphoid features. CML-BP responds poorly to treatment and is usually fatal. This review discusses the role of genomic instability leading to blastic transformation of CML and proposes some novel therapeutic approaches.