Effective Targeting of Quiescent Chronic Myelogenous Leukemia Stem Cells by Histone Deacetylase Inhibitors in Combination with Imatinib Mesylate

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2010 May 19

PMID 20478526

Citations 118

Authors

Bin Zhang

Adam C Strauss

Su Chu

Min Li

Yinwei Ho

Keh-Dong Shiang

David S Snyder

Claudia S Huettner

Leonard Shultz

Tessa Holyoake

Ravi Bhatia

Affiliations

Soon will be listed here.

Abstract

Imatinib mesylate (IM) induces remission in chronic myelogenous leukemia (CML) patients but does not eliminate leukemia stem cells (LSCs), which remain a potential source of relapse. Here we investigated the ability of HDAC inhibitors (HDACis) to target CML stem cells. Treatment with HDACis combined with IM effectively induced apoptosis in quiescent CML progenitors resistant to elimination by IM alone, and eliminated CML stem cells capable of engrafting immunodeficient mice. In vivo administration of HDACis with IM markedly diminished LSCs in a transgenic mouse model of CML. The interaction of IM and HDACis inhibited genes regulating hematopoietic stem cell maintenance and survival. HDACi treatment represents an effective strategy to target LSCs in CML patients receiving tyrosine kinase inhibitors.

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