BCR-ABL kinase is dead; long live the CML stem cell.
BCR-ABL kinase is dead; long live the CML stem cell.
复制标题
BCR-ABL 激酶已死亡；
DOI：
10.1172/jci43605
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Carroll,Martin
中科院分区：
文献类型：
--
作者：
Perl,Alexander;Carroll,Martin
慢性粒细胞白血病（CML）是一种以骨髓血细胞扩增为特征的造血系统疾病。它是由t（9;22）染色体易位导致融合酪氨酸激酶BCR-ABL的表达引起的，酪氨酸激酶抑制剂（TKI）治疗可导致长期缓解，但患者仍保持BCR-ABL+。人们一致认为TKI不会杀死CML干细胞;然而，这是因为CML干细胞中缺乏BCR-ABL激酶抑制还是因为CML干细胞不需要BCR-ABL才能生存，这一点存在争议。在本期的JCI中，Corbin及其同事提供了明确的证据，证明BCR-ABL在CML干细胞中具有激酶活性，TKI抑制这种激酶活性而不影响CML干细胞的存活。相反，CML干细胞恢复到正常的依赖细胞因子的生存和增殖。这些结果表明，CML干细胞不是BCR-ABL成瘾，并对开发CML的治愈性治疗方法具有重要意义。
Chronic myeloid leukemia (CML) is a hematopoietic disease characterized by expansion of myeloid blood cells. It is caused by the t(9;22) chromosomal translocation that results in the expression of the fusion tyrosine kinase BCR-ABL. Tyrosine kinase inhibitor (TKI) therapy has led to long-term remissions, but patients remain BCR-ABL+. There is agreement that TKIs do not kill CML stem cells; however, it is controversial whether this is because of a lack of BCR-ABL kinase inhibition in CML stem cells or because CML stem cells do not require BCR-ABL for survival. In this issue of theJCI, Corbin and colleagues provide definitive evidence that BCR-ABL is kinase active in CML stem cells and that TKIs inhibit this kinase activity without affecting CML stem cell survival. Rather, CML stem cells revert to a normal dependence on cytokines for survival and proliferation. These results demonstrate that the CML stem cell is not BCR-ABL addicted and have important implications for developing curative therapeutic approaches to CML.