4.3 Article

β-Catenin and AKT are promising targets for combination therapy in acute myeloid leukemia

Journal

LEUKEMIA RESEARCH
Volume 37, Issue 10, Pages 1329-1340

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2013.06.023

Keywords

Acute myeloid leukemia; Homoharringtonine; Aclarubicin; Synergistic; beta-Catenin

Funding

  1. National Natural Science Foundation of China [81070418]
  2. Zhejiang Provincial Science and Technology Foundation of China [2012C33G2010243]

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In this study, we confirmed that combining HHT with ACR can result in synergistic cytotoxicity to AML cells in vitro and in vivo. Combining HHT and ACR simultaneously inhibited PI3K/AKT and WNT/beta-catenin signaling in AML cells. Significant increases in growth inhibition and apoptosis were induced by an AKT inhibitor when the WNT3A gene of THP-1 cells was silenced. HHT + ACR could synergistically induce the apoptosis of CD34(+)/CD38(-) primary AML cells. These results highlight beta-catenin and AKT are promising targets for combination therapy for AML. (C) 2013 Elsevier Ltd. All rights reserved.

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