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Medline ® Abstract for Reference 19

of 'Cellular and molecular biology of chronic myeloid leukemia'

19
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BCR-ABL kinase is dead; long live the CML stem cell.
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Perl A, Carroll M
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J Clin Invest. 2011;121(1):22. Epub 2010 Dec 13.
 
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.
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Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
PMID