A novel vitamin D gene therapy for acute myeloid leukemia.

ABSTRACT: Current treatment approaches for older adult patients with acute myeloid leukemia (AML) are often toxic and lack efficacy. Active vitamin D3 (1,25(OH)₂D3) has been shown to induce myeloid blast differentiation but at concentrations that have resulted in unacceptable, off-target hypercalcemia in clinical trials. In our study, we found that the combination of 1,25(OH)₂D3 and the hypomethylating agent (HMA) 5-Azacytidine (AZA) enhanced cytotoxicity and differentiation, and inhibited proliferation of several AML cell lines (MOLM-14, HL60) and primary AML patient samples. This observation was corroborated by our RNA sequence analysis data in which VDR, CD14, and BAX expression were increased, and FLT-3, PIM1 and Bcl-2 expression were decreased. To address the hypercalcemia

SUBMITTER: Xu Y 

PROVIDER: S-EPMC7509076 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature