Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy.
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.
Abe
Akihiro
A
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.
Minami
Yosuke
Y
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.
Hayakawa
Fumihiko
F
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Kitamura
Kunio
K
Department of Hematology, Ichinomiya Municipal Hospital, Ichinomiya, Japan.
Nomura
Yuka
Y
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Murata
Makoto
M
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Katsumi
Akira
A
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Kiyoi
Hitoshi
H
Department of Infectious Disease, Nagoya University School of Medicine, Nagoya, Japan.
Jamieson
Catriona H M
CHM
Division of Hematology-Oncology, Department of Medicine and Moores Cancer Center, University of California at San Diego School of Medicine, La Jolla, CA, USA.
Wang
Jean Y J
JYJ
Division of Hematology-Oncology, Department of Medicine and Moores Cancer Center, University of California at San Diego School of Medicine, La Jolla, CA, USA.
Naoe
Tomoki
T
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
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
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