Effect of imatinib mesylate on chronic myelogenous leukemia hematopoietic progenitor cells.
Treatment of chronic myelogenous leukemia (CML) has been greatly enhanced by the development of Imatinib mesylate, a specific inhibitor of the BCR/ABL tyrosine kinase. While it is clear that imatinib effectively targets BCR/ABL positive hematopoietic cells, studies examining its effect on primitive hematopoietic progenitors are much more limited. As CML arises in a primitive hematopoietic progenitor cell, it is especially important to understand the effect of imatinib on these cells. Here we review studies investigating the effect of imatinib on the proliferation and viability of primitive and committed hematopoietic progenitors in CML. We describe evidence that BCR/ABL positive progenitors may persist in patients responding to imatinib and discuss problems of resistance to imatinib. Finally we discuss studies evaluating new approaches to overcome resistance of CML progenitor cells to imatinib.
Holtz
Melissa S
MS
Division of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
Bhatia
Ravi
R
D018952:Antigens, CD34 / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D013234:Stem Cells / Q000378:metabolism
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl