Lysine specific demethylase 1 inactivation enhances differentiation and promotes cytotoxic response when combined with all-trans retinoic acid in acute myeloid leukemia across subtypes.

ABSTRACT: Lysine specific demethylase 1 (LSD1) is a histone modifying enzyme that suppresses gene expression through demethylation of lysine 4 on histone H3. The anti-tumor activity of GSK2879552 and GSK-LSD1, potent, selective irreversible inactivators of LSD1, has previously been described. Inhibition of LSD1 results in a cytostatic growth inhibitory effect in a range of acute myeloid leukemia cell lines. To enhance the therapeutic potential of LSD1 inhibition in this disease setting, a combination of LSD1 inhibition and all-trans retinoic acid was explored. All-trans retinoic acid is currently approved for use in acute promyelocytic leukemia in which it promotes differentiation of abnormal blast cells into normal white blood cells. Combined treatment with all-trans retinoic a

SUBMITTER: Smitheman KN 

PROVIDER: S-EPMC6545850 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature