Paul O'Gorman Leukaemia Research Centre, Institute for Cancer Sciences, University of Glasgow, 21 Shelley Road, G12 0ZD Glasgow, UK.
Curr Hematol Malig Rep. 2011 Jun;6(2):82-7. doi: 10.1007/s11899-011-0085-y.
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder that is characterized by the presence of a fusion oncogene, BCR-ABL, which encodes a protein with constitutive tyrosine kinase activity. This activity causes excessive production of myeloid cells and their premature release into the circulation. The discovery of tyrosine kinase inhibitors marked a major advance in CML therapy, but these drugs cannot eradicate the disease because they are unable to kill the most primitive, quiescent leukemic stem cells. This review discusses current research in CML and attractive targets that have emerged with potential for eradicating the disease. Several new targets have recently been investigated as potential modulators in myeloid leukemia pathogenesis, including the multiple gene regulators miRNAs, the apparently leukemia-specific cell surface marker IL1RAP, transcription factors such as BMI1 and FOXOs, the tumor suppressors PML and PP2A, and the tyrosine kinase JAK2.
慢性髓细胞白血病（CML）是一种克隆性骨髓增殖性疾病，其特征在于存在融合癌基因 BCR-ABL，该基因编码具有组成性酪氨酸激酶活性的蛋白质。这种活性导致髓样细胞的过度产生及其过早释放到循环中。酪氨酸激酶抑制剂的发现标志着 CML 治疗的重大进展，但这些药物不能根除疾病，因为它们无法杀死最原始的静止白血病干细胞。这篇综述讨论了 CML 的当前研究和有希望的靶点，这些靶点有可能根除该疾病。最近，一些新的靶点已被研究为髓性白血病发病机制的潜在调节剂，包括多个基因调节剂 miRNA、明显的白血病特异性细胞表面标记物 IL1RAP、转录因子如 BMI1 和 FOXOs、肿瘤抑制因子 PML 和 PP2A 以及酪氨酸激酶 JAK2。
