Sorafenib Inhibition of Mcl-1 Accelerates ATRA-Induced Apoptosis in Differentiation-Responsive AML Cells.

ABSTRACT:

Purpose

All trans-retinoic acid (ATRA) is successful in treating acute promyelocytic leukemia (APL) by inducing terminal differentiation-mediated cell death, but it has limited activity in non-APL acute myeloid leukemia (AML). We aim to improve ATRA therapy of AML by enhancing apoptosis through repression of the antiapoptotic proteins Bcl-2 and Mcl-1.

Experimental design

APL and AML cell lines, as well as primary AML samples, were used to explore the mechanisms regulating differentiation and apoptosis during ATRA treatment. Stable transfection and gene silencing with siRNA were used to identify the key factors that inhibit apoptosis during induction of differentiation and drugs that accelerate apoptosis.

Results

In differentiation-responsive AML cells, ATRA treatment

SUBMITTER: Wang R 

PROVIDER: S-EPMC4775303 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature