论文部分内容阅读
核心结合因子相关性急性髓细胞白血病(core binding factor-acute myeloid leukemia,CBF-AML)发病机制是近十几年来在白血病领域研究较多的一个热点。在CBF-AML中,分子预后标志c-KIT,RAS等酪氨酸激酶的研究较为广泛,这些激酶的异常激活会在细胞水平引起细胞增殖能力的提高而延长细胞存活期,另外CBF融合转录因子会使细胞失去分化能力,两者结合起来会诱使CBF-AML发生发展,因此控制这些激酶活性或者抑制下游通路是治疗CBF-AML的关键所在。酪氨酸激酶抑制剂达沙替尼曾经主要应用于慢性粒细胞白血病,目前正尝试应用于伴有t(8;21)(q22;q22)染色体移位AML-M2,有报道达沙替尼联合AKT抑制剂可明显改善CBF-AML患者病情。芽孢中间球菌核酸核酶(Binase)对AML-M2中Kasumi-1细胞毒性作用也逐渐成为研究的热点。
The pathogenesis of core binding factor-associated acute myeloid leukemia (CBF-AML) has been a hot spot in the field of leukemia for more than ten years. In CBF-AML, the molecular prognostic markers c-KIT, RAS and other tyrosine kinase research is more extensive, abnormal activation of these kinases at the cellular level caused by increased cell proliferation and prolong cell survival, the other CBF fusion transcription factor Will lose the ability of cells to differentiate, and the combination of the two will induce the development of CBF-AML. Therefore, controlling the activity of these kinases or inhibiting downstream pathways is the key to CBF-AML treatment. Dasatinib, a tyrosine kinase inhibitor, has been used predominantly in chronic myeloid leukemia and is currently being tested on AML-M2 associated with t (8; 21) (q22; q22) chromosomal translocation. Dasatinib Combination of AKT inhibitors can significantly improve the condition of CBF-AML patients. The toxic effect of Binase on Kasumi-1 cells in AML-M2 has also become a hot research topic.