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Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy

starliu 添加于 2009-10-14 22:08 | 1551 次阅读 | 0 个评论

作者
Abe A, Minami Y, Hayakawa F, Kitamura K, Nomura Y, Murata M, Katsumi A, Kiyoi H, Jamieson CHM, Wang JYJ, Naoe T
摘要
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.
详细资料
- 关键词: Adult; Female; Fusion Proteins, bcr-abl/antagonists & inhibitors/*metabolism; Hematopoietic Stem Cells/*metabolism/pathology; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/*enzymology/pathology; Male; Middle Aged; Neoplasm, Residual/enzymology/pathology; Neoplastic Stem Cells/*metabolism/pathology; Piperazines/*administration & dosage; Protein Kinase Inhibitors/*administration & dosage; Protein-Tyrosine Kinases/antagonists & inhibitors/*metabolism; Pyrimid
- 文献种类:期刊
- 期刊名称: International Journal of Hematology
- 期刊缩写: Int J Hematol
- 期卷页: 2008年第88卷第5期 471-475页
- 地址: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. aakihiro@med.nagoya-u.ac.jp
- ISBN: 1865-3774
- 备注:PMID:19039626
标签

leukaemia chronic myeloid
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