核心结合因子相关性急性髓细胞白血病发病机制的研究进展

Research progress of the pathogenesis of core binding factor-related acute myeloid leukemia

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。

Abstract：The pathogenesis of core binding factor-related acute myeloid leukemia （CBF-AML） is a hotspot in the study of leukemia in the past decade. The research of CBF-AML is focused on the molecular prognostic markers c-KIT, RAS and other tyrosine kinases. Extensive abnormal activation of these kinases in cellular level causes increased cell proliferation, cell survival and growth, and CBF fusion transcription factors cause cells to lose their ability to differentiate. The combination of two factors could induce development of CBF-AML. Thereby controlling the activity of these kinases or inhibiting downstream pathway becomes very important to cure this disease. Initially, the tyrosine kinase inhibitor dasatinib has primarily been used in chronic myeloid leukemia, and now it is tried to apply in the treatment of t （8; 21） （q22; q22） chromosome shift AML-M2. Several reports have shown that combination of AKT inhibitor with dasatinib can significantly improve the survival ratio in CBF-AML patients. RNase from Bacillus intermedius is toxic to AML-M2 type Kasumi-1 cells; this is becoming a hot in this research field.