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.
Alexander Perl, Martin Carroll
Title and authors | Publication | Year |
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BCR-ABL disrupts PTEN nuclear-cytoplasmic shuttling through phosphorylation-dependent activation of HAUSP
A Morotti, C Panuzzo, S Crivellaro, B Pergolizzi, U Familiari, AH Berger, G Saglio, PP Pandolfi |
Leukemia | 2013 |
The matricellular protein CCN3 regulates NOTCH1 signalling in chronic myeloid leukaemia
Suresh S, McCallum L, Crawford LJ, Lu WH, Sharpe DJ, Irvine AE |
The Journal of Pathology | 2013 |