Eradication of Central Nervous System Leukemia of T-Cell Origin with a Brain-Permeable LSD1 Inhibitor.

ABSTRACT:

Purpose

Lysine-specific demethylase 1 (LSD1) regulates several biological processes via the bifunctional modulation of enhancer functions. Recently, we reported that LSD1 overexpression is a founder abnormality of T-cell leukemogenesis and is maintained in fully transformed T-cell acute lymphoblastic leukemia (T-ALL) cells. On the basis of this finding, we attempted to develop novel LSD1 inhibitors effective for T-ALL with central nervous system (CNS) involvement.

Experimental design

We chemically modified the prototype LSD inhibitor tranylcypromine (TCP) and screened for cytotoxicity against TCP-resistant T-ALL cell lines. In vivo efficacy of novel LSD1 inhibitors was examined in immunodeficient mice transplanted with luciferase-expressing T-ALL cell lines, which fai

SUBMITTER: Saito S 

PROVIDER: S-EPMC6397674 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature