University of Glasgow, Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, G12 0YN, UK.
Curr Hematol Malig Rep. 2013 Mar;8(1):14-21. doi: 10.1007/s11899-012-0148-8.
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder that is characterized by the presence of the fusion oncogene BCR-ABL that encodes the tyrosine kinase BCR-ABL. Constitutive expression of BCR-ABL leads to the unregulated production of mature myeloid cells in the bone marrow and their subsequent release into the blood. Untreated, CML will progress from a chronic to accelerated phase over a number of years before quickly proceeding to a terminal blast crisis phase, reminiscent of acute leukemia. The advent of tyrosine kinase inhibitors has led to much improved management of the disease, but these drugs do not provide a cure as they are unable to eradicate the most primitive, quiescent fraction of CML stem cells. This review looks at recent research into targeting CML stem cells and focuses on major signalling pathways of interest.
慢性髓细胞白血病(CML)是一种克隆性骨髓增生性疾病,其特征是存在融合癌基因 BCR-ABL,该基因编码酪氨酸激酶 BCR-ABL。BCR-ABL 的组成性表达导致骨髓中未成熟髓细胞的不受调节产生,并随后释放到血液中。未经治疗,CML 将在数年内从慢性期进展为加速期,然后迅速进展为终末期爆发性危机期,类似于急性白血病。酪氨酸激酶抑制剂的出现极大地改善了该疾病的治疗效果,但这些药物并不能治愈疾病,因为它们无法清除 CML 干细胞中最原始、静止的部分。这篇综述探讨了最近针对 CML 干细胞的研究,并重点关注了主要的信号通路。