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

The anti-apoptotic proteins Bcl-X(L) 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...

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Detalles Bibliográficos
Autores principales: Baev, Denis V., Krawczyk, Janusz, O׳Dwyer, Michael, Szegezdi, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
Materias:
Case Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216386/
https://www.ncbi.nlm.nih.gov/pubmed/25379408
http://dx.doi.org/10.1016/j.lrr.2014.06.001
Descripción
Sumario:The anti-apoptotic proteins Bcl-X(L) 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.

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