The BH3-mimetic ABT-737 effectively kills acute myeloid leukemia initiating cells

• Main Authors: Denis V. Baev, Janusz Krawczyk, Michael O׳Dwyer, Eva Szegezdi
• Format: Article
• Language: English
• Published: Elsevier 2014-01-01
• Series: Leukemia Research Reports
• Subjects: Acute myeloid leukemia; Putative leukemic stem cells; CD34+/CD38−; ABT-737; BH3-mimetic
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213048914000120

The anti-apoptotic proteins Bcl-XL and Bcl-2 are abundantly expressed in hematopoietic stem cells and/or progenitor cells. Furthermore, leukemic cells expressing these proteins are enriched in minimal residual disease cell populations. This prompted us to test the BH3-mimetic compound ABT-737 for its ability to eradicate putative leukemic stem cells. ABT-737 demonstrated potent cytotoxic effects in all patient samples tested. The efficacy of ABT-737 against AML blasts and the primitive CD34+/CD38− population was equal and independent of sensitivity to cytarabine/daunorubicin. These results, together with previously reported synergistic effects of ABT-737 with chemotherapeutics make BH3-mimetics promising candidates for future AML treatment regimens.