title: BCR-ABL kinase is dead; long live the CML stem cell.
abstract: Chronic myeloid leukemia (CML) is a hematopoietic disease characterized by expansion of myeloid blood cells. It is caused by the t(9;22) chromosomal translocation that results in the expression of the fusion tyrosine kinase BCR-ABL. Tyrosine kinase inhibitor (TKI) therapy has led to long-term remissions, but patients remain BCR-ABL+. There is agreement that TKIs do not kill CML stem cells; however, it is controversial whether this is because of a lack of BCR-ABL kinase inhibition in CML stem cells or because CML stem cells do not require BCR-ABL for survival. In this issue of the JCI, Corbin and colleagues provide definitive evidence that BCR-ABL is kinase active in CML stem cells and that TKIs inhibit this kinase activity without affecting CML stem cell survival. Rather, CML stem cells revert to a normal dependence on cytokines for survival and proliferation. These results demonstrate that the CML stem cell is not BCR-ABL addicted and have important implications for developing curative therapeutic approaches to CML.
authors.affiliation: Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Perl
authors.forename: Martin
authors.initials: M
authors.lastname: Carroll
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl