Effective Targeting of Quiescent Chronic Myelogenous Leukemia Stem Cells by Histone Deacetylase Inhibitors in Combination with Imatinib Mesylate
| Autor: | Leonard D. Shultz, Adam C. Strauss, Tessa L. Holyoake, YinWei Ho, Keh-Dong Shiang, Bin Zhang, Su Chu, Min Li, Claudia S. Huettner, Ravi Bhatia, David S. Snyder |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Fusion Proteins bcr-abl Antineoplastic Agents Apoptosis Mice Transgenic CELLCYCLE Article Piperazines 03 medical and health sciences Myelogenous Mice 0302 clinical medicine hemic and lymphatic diseases Leukemia Myelogenous Chronic BCR-ABL Positive medicine Animals Humans Progenitor cell neoplasms 030304 developmental biology Cell Proliferation 0303 health sciences business.industry Hematopoietic stem cell Cell Biology DNA medicine.disease STEMCELL 3. Good health Histone Deacetylase Inhibitors Leukemia Imatinib mesylate medicine.anatomical_structure Pyrimidines Oncology 030220 oncology & carcinogenesis Benzamides Cancer research Imatinib Mesylate Neoplastic Stem Cells Stem cell business Tyrosine kinase Chronic myelogenous leukemia |
| Popis: | SummaryImatinib 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. |
| Databáze: | OpenAIRE |
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