title: Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. aakihiro@med.nagoya-u.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Abe
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.|Division of Hematology-Oncology, Department of Medicine and Moores Cancer Center, University of California at San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Minami
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hayakawa
authors.affiliation: Department of Hematology, Ichinomiya Municipal Hospital, Ichinomiya, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Kitamura
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nomura
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Katsumi
authors.affiliation: Department of Infectious Disease, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kiyoi
authors.affiliation: Division of Hematology-Oncology, Department of Medicine and Moores Cancer Center, University of California at San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: Catriona H M
authors.initials: CHM
authors.lastname: Jamieson
authors.affiliation: Division of Hematology-Oncology, Department of Medicine and Moores Cancer Center, University of California at San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: Jean Y J
authors.initials: JYJ
authors.lastname: Wang
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000328:Adult; D001549:Benzamides; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000201:enzymology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism*; D012074:Remission Induction; D013997:Time Factors
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl