HDAC inhibitor suppresses proliferation and tumorigenicity of drug-resistant chronic myeloid leukemia stem cells through regulation of hsa-miR-196a targeting BCR/ABL1

Experimental Cell Research
Oluwaseun Adebayo BamoduChi-Tai Yeh

Abstract

Failure to eradicate hematologic cancer stem cells (hCSCs) associated with resistance to tyrosine kinase inhibitors such as imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients is a clinical challenge that highlights the need for discovering and developing therapeutic strategies that target and eliminate these hCSCs. Herein, we document the essential role of the interplay between histone deacetylases (HDACs), the polycomb group proteins, pluripotency transcription factors and the cell cycle machinery in the viability, oncogenicity and therapy evasion of IM-resistant CD34+/CD38- CML stem cells (CML-SCs). Using the proteotranscriptomic analyses of wild type (WT), CD34+/CD38+ and CD34+/CD38- K562 or KU812 cells, we showed that CD34+/CD38- SC-enriched cells expressed significantly higher levels of CD44, CD133, SOX2, Nanog, OCT4, and c-Myc mRNA and/or protein, compared to the WT or CD34+/CD38+ cells. This overexpression of stemness factors in the CD34+/CD38- cells positively correlates with enhanced expression of HDACs 1-6, cyclins D1/D3, CDK 2, 4 and 6, while inversely correlating with p18, p21 and p27. Enhanced co-expression of MDR1, survivin, and Bcl-2 proteins, supposedly involved in IM-resistance and CML-SC surviva...Continue Reading

Citations

Feb 6, 2020·Cancers·Hélène LossonMarc Diederich
Sep 8, 2020·Journal of Zhejiang University. Science. B·Nan WenZheng-Gui Du
Jan 8, 2019·F1000Research·Ellen G JarredPatrick S Western
Jul 22, 2020·Stem Cell Reviews and Reports·Neerada Meenakshi WarrierPraveen Kumar
Mar 25, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Ismail S MohiuddinMin H Kang

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