Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy
Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy
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DOI：
10.1007/s12185-008-0221-1
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发表时间：
2008-12-01
影响因子：
2.1
通讯作者：
Naoe, Tomoki
中科院分区：
文献类型：
--
作者：
Abe, Akihiro;Minami, Yosuke;Naoe, Tomoki
甲磺酸伊马替尼（IM）可有效治疗慢性粒细胞白血病（CML），IM是一种BCR-ABL酪氨酸激酶的小分子抑制剂，在CML患者的整个造血区室（包括干细胞（HSC）和祖细胞）中表达。虽然IM诱导疾病缓解，但似乎并不能根除BCR-ABL阳性干细胞。我们研究了IM治疗后使用荧光激活细胞分选法分离的HSC和髓系祖细胞中残留的CML细胞。实时定量聚合酶链反应检测BCR-ABL转录本显示CML祖细胞在12个月内被根除，而BCR-ABL阳性的HSC仍然存在。然而，在HSC人群中，IM治疗持续可显著降低BCR-ABL与BCR的比值。我们的研究结果表明，分选和纯化的干细胞是有用的BCR-ABL阳性微小残留病的更灵敏的定量。
Chronic myelogenous leukemia (CML) is effectively treated with imatinib mesylate (IM), a small molecule inhibitor of the BCR-ABL tyrosine kinase that is expressed in the entire hematopoietic compartment including stem cells (HSC) and progenitors in CML patients. While IM induces disease remission, it does not appear to eradicate BCR-ABL-positive stem cells. We investigated the residual CML cells in HSC and myeloid progenitors isolated using fluorescence-activated cell sorting after IM-therapy. Quantitative real-time polymerase chain reaction detecting BCR-ABL transcripts showed that CML progenitors were eradicated within 12 months while the BCR-ABL- positive HSC remained. However, IM-therapy continuation could significantly decrease the ratio of BCR-ABL to BCR also in the HSC population. Our results implicate that the sorted and purified stem cells are useful for more sensitive quantification of BCR-ABL- positive minimal residual disease.