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Acute Non-Lymphocytic Leukemias

The novel triterpenoid CDDO-Me suppresses MAPK pathways and promotes p38 activation in acute myeloid leukemia cells

Leukemia volume 19, pages 1350–1354 (2005)Cite this article

Abstract

Development of novel therapeutic strategies is a continuing challenge for the treatment of acute myeloid leukemia (AML). The novel triterpenoid, C-28 methyl ester of 2-cyano-3,12-dioxoolen-1,9-dien-28-oic acid (CDDO-Me), induces apoptosis in myeloid leukemic cell lines and in primary AML samples. In this report, the effects of CDDO-Me on CD34+ AML progenitor cells in vitro were examined. CDDO-Me induced apoptosis in all but one of ten AML samples. CDDO-Me is known to inhibit the activation of ERK1/2. In this series of primary AML samples, ERK was expressed and phosphorylated in all patient samples studied and CDDO-Me inhibited ERK phosphorylation in five of 10 samples. However, CDDO-Me induced apoptosis in four of five samples without decreasing pERK levels, suggesting that pERK is not the sole target of the compound. CDDO-Me induced phosphorylation of p38 in AML-derived U937 cells. Pretreatment of U937 cells with a p38 inhibitor protected cells from the cyto-toxic effects of CDDO-Me. These findings suggest a role for p38 in CDDO-Me-induced apoptosis. In preliminary studies, CDDO-Me induced p38 phosphorylation in seven of eight primary AML samples. These findings suggest that CDDO-Me treatment shifts cell signaling away from cyto-protective pathways and thus CDDO-Me may be effective for the treatment of AML.

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Acknowledgements

This research was supported by Leukemia and Lymphoma Society (MK) and the National Institutes of Health RO1 CA089346 (MA).

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Authors and Affiliations

  1. Department of Blood and Marrow Transplantation, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Konopleva, R Contractor, W Chen & M Andreeff

  2. Division of Cell Signaling, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA

    S M Kurinna & P P Ruvolo

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  1. M Konopleva
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  2. R Contractor
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  3. S M Kurinna
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  4. W Chen
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  5. M Andreeff
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  6. P P Ruvolo
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Correspondence to P P Ruvolo.

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Konopleva, M., Contractor, R., Kurinna, S. et al. The novel triterpenoid CDDO-Me suppresses MAPK pathways and promotes p38 activation in acute myeloid leukemia cells. Leukemia 19, 1350–1354 (2005). https://doi.org/10.1038/sj.leu.2403828

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  • DOI: https://doi.org/10.1038/sj.leu.2403828

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