Effective targeting of quiescent chronic myelogenous leukemia stem cells by histone deacetylase inhibitors in combination with imatinib mesylate.
Document Type
Article
Publication Date
2010
Keywords
Apoptosis, Cell-Proliferation, Fusion-Proteins-bcr-abl, Histone-Deacetylase-Inhibitors, Leukemia-Myelogenous-Chronic-BCR-ABL-Positive, Mice-Transgenic, Neoplastic-Stem-Cells, Piperazines, Pyrimidines
First Page
427
Last Page
442
JAX Source
Cancer Cell 2010 May; 17(5):427-42.
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.
Recommended Citation
Zhang B,
Strauss AC,
Chu S,
Li M,
Ho Y,
Shiang KD,
Snyder DS,
Huettner CS,
Shultz L,
Holyoake T,
Bhatia R.
Effective targeting of quiescent chronic myelogenous leukemia stem cells by histone deacetylase inhibitors in combination with imatinib mesylate. Cancer Cell 2010 May; 17(5):427-42.