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

Denis V. Baev
, Janusz Krawczyk
, Michael O'Dwyer
, Eva Szegezdi

Medicine

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

20 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	79-82
Number of pages	4
Journal	Leukemia Research Reports
Volume	3
Issue number	2
DOIs	https://doi.org/10.1016/j.lrr.2014.06.001
Publication status	Published - 1 Sep 2014

Keywords

ABT-737
Acute myeloid leukemia
BH3-mimetic
CD34/CD38
Putative leukemic stem cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.lrr.2014.06.001

Cite this

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title = "The BH3-mimetic ABT-737 effectively kills acute myeloid leukemia initiating cells",

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.",

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T1 - The BH3-mimetic ABT-737 effectively kills acute myeloid leukemia initiating cells

AU - Baev, Denis V.

AU - Krawczyk, Janusz

AU - O'Dwyer, Michael

AU - Szegezdi, Eva

PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.

AB - 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.

KW - ABT-737

KW - Acute myeloid leukemia

KW - BH3-mimetic

KW - CD34/CD38

KW - Putative leukemic stem cells

UR - https://www.scopus.com/pages/publications/84907553868

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DO - 10.1016/j.lrr.2014.06.001

M3 - Article

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JO - Leukemia Research Reports

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ER -

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

Abstract

Keywords

UN SDGs

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