Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Curr Hematol Malig Rep. 2012 Jun;7(2):87-93. doi: 10.1007/s11899-012-0114-5.
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.
BCR-ABL1 致癌酪氨酸激酶可使多能造血干细胞发生转化，引发慢性髓性白血病慢性期（CML-CP），这是一种以成熟髓性细胞过度积累为特征的骨髓增殖性疾病。CML-CP 患者通常对 ABL1 酪氨酸激酶抑制剂（TKI）治疗有反应，如伊马替尼，但一些初始反应的患者可能会随后产生耐药性。CML-CP 白血病干细胞（LSCs）本身对 TKI 不敏感，因此可以长期存活。这些 LSCs 或其后代可能在某个阶段获得额外的遗传变化，导致白血病进一步转化，从 CML-CP 进展到更晚期，这已被细分为加速期（CML-AP）或急变期（CML-BP）。CML-BP 的特征是不成熟祖细胞的主要克隆性扩张，这些祖细胞具有髓性或淋巴样特征。CML-BP 对治疗反应不佳，通常是致命的。这篇综述讨论了导致 CML 急变的基因组不稳定性的作用，并提出了一些新的治疗方法。
