Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia [Illumina HumanHT-12 gene expression array]

ABSTRACT: All-trans-retinoic acid (ATRA) has been successfully used in therapy of acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML) but the response of non-APL AML cases to ATRA-based treatment has been poor. Here we show that, via epigenetic reprogramming, inhibitors of LSD1/KDM1 demethylase including tranylcypromine (TCP) unlocked the ATRA-driven therapeutic response in non-APL AML. LSD1 inhibition did not lead to an increase in genome-wide H3 lysine4 dimethylation (H3K4me2) but did increase H3K4me2 and expression of myeloid differentiation-associated genes. Importantly, treatment with ATRA plus TCP dramatically diminished engraftment of primary human AML cells in vivo in NOD.SCID mice, suggesting that ATRA in combination with TCP may target leu

ORGANISM(S): Homo sapiens

SUBMITTER: Hans-Ulrich Klein 

PROVIDER: E-GEOD-34672 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress