Protein Nanomedicine Exerts Cytotoxicity toward CD34+ CD38- CD123+ Leukemic Stem Cells
Parwathy Chandran1, Keechilat Pavithran2, Neeraj Sidharthan2
1Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India.
Abstract:
The efficacy of protein-vorinostat nanomedicine (NV) is demonstrated in leukemic stem cells (LSC) isolated from refractory acute myeloid leukemia (AML) patient samples, where it successfully ablated both CD34+ CD38- CD123+ LSC and non-LSC "leukemic blast" compartments, without inducing myelosuppression or hemotoxicity. Besides, NV also exerted excellent synergistic lethality against leukemic bone marrow cells (BMC) at lower concentrations (0.1 μM) in combination with DNA methyltransferase (DNMT) inhibitor, decitabine. Considering the extermination of resilient LSC and synergism with decitabine, NV shows promise for clinical translation in the setting of a more tolerable and effective epigenetic targeted therapy for leukemia.
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