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

Denis V Baev; Janusz Krawczyk; Michael O׳Dwyer; Eva Szegezdi

doi:10.1016/j.lrr.2014.06.001

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

Leuk Res Rep. 2014 Sep 1;3(2):79-82. doi: 10.1016/j.lrr.2014.06.001. eCollection 2014.

Authors

Denis V Baev¹, Janusz Krawczyk², Michael O׳Dwyer³, Eva Szegezdi¹

Affiliations

¹ Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Biosciences, Dangan, Galway, Ireland.
² Department of Hematology, University Hospital Galway, Newcastle Road, Galway, Ireland.
³ Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Biosciences, Dangan, Galway, Ireland ; Department of Hematology, University Hospital Galway, Newcastle Road, Galway, Ireland.

Abstract

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.

Keywords: ABT-737; Acute myeloid leukemia; BH3-mimetic; CD34+/CD38−; Putative leukemic stem cells.