BCR-ABL kinase is dead; long live the CML stem cell

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 lull 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