Journal
LEUKEMIA RESEARCH
Volume 34, Issue 2, Pages 235-242Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2009.05.014
Keywords
Valproic acid; SDF-1/CXCR4 axis; Chemotaxis; AML; HDAC inhibitors
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Funding
- Canadian Blood Services(CBS)/Canadian Institutes for Health Research Blood Utilization and Conservation Initiative [XE00023, XE00025]
- CBS
- Heart and Stroke Foundation
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We recently reported that the histone deacetylase inhibitor, valproic acid (VPA), increases CXCR4 receptor expression and function in cord blood hematopoietic stem/progenitor cells (HSPC) and the immature, highly CD34-positive AML cell lines KG-1a and KG-1. In this study, we investigated whether VPA influences CXCR4 in CD34-negative AML cell lines (promyelocytic HL-60 and monocytic THP-1), as well as both CD34-positive and CD34-negative primary AML cells. We found that VPA (i) diminishes CXCR4 expression and chemotaxis in HL-60 cells and in the CD34-negative subtypes of primary AML cells and (ii) increases CXCR4 expression and function in the highly CD34-positive subtypes of primary AML cells. Hence, we suggest that VPA exerts different effects on CXCR4 depending on cell maturation status, and this novel finding may have important implications for AML therapy. (C) 2009 Elsevier Ltd. All rights reserved.
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