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Title of Journal: Int J Hematol

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Abbravation: International Journal of Hematology

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Springer Japan

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DOI

10.1016/0921-4526(94)91925-9

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1865-3774

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Expanded distribution of the T315I mutation among

Authors: Yosuke Minami Tomohiro Kajiguchi Akihiro Abe Toshihito Ohno Hitoshi Kiyoi Tomoki Naoe
Publish Date: 2010/10/22
Volume: 92, Issue: 4, Pages: 664-666
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Abstract

T315I mutation of the ABLkinase domain in chronic myeloid leukemia CML confers resistance to imatinib IM as well as secondgeneration tyrosine kinase inhibitors TKIs We report a chronicphase CML patient undergoing IM treatment who showed the overt existence of the T315I mutation after 15 months We retrospectively analyzed the distribution of the T315I mutation using the invader assay and direct DNA sequencing among FACSAriasorted populations from bone marrow cells total mononuclear cells TMC hematopoietic stem cells HSC/Thy1+ HSC/Thy1− common myeloid progenitors CMP granulocyte macrophage progenitors GMP and megakaryocyte erythroid progenitors MEP at 0 3 6 9 and 12 months after IM treatment T315I was barely detectable by 12 months in TMC but detectable in 192 of HSC/Thy1− and 464 of MEP at diagnosis and finally expanded into all populations These results suggest that the monitoring of gene mutations in HSC and progenitors at diagnosis might be helpful for the early detection of TKIresistant CML patients and facilitate appropriate therapeutic decisionWe thank Yuka Nomura at Nagoya University for her technical assistance This study was supported by GrantsinAid from the National Institute of Biomedical Innovation and from the Ministry of Education Culture Sports Science and Technology on Scientific Research

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