ATRA-induced Upregulation of Beclin 1 Prolongs the Life Span of Differentiated Acute Promyelocytic Leukemia Cells

Overview

Journal Autophagy

Specialty Cell Biology

Date 2011 Jun 22

PMID 21691148

Citations 31

Authors

Aurore Trocoli

Julie Mathieu

Muriel Priault

Josy Reiffers

Sylvie Souquere

Gerard Pierron

Francoise Besancon

Mojgan Djavaheri-Mergny

Affiliations

Soon will be listed here.

Abstract

Acute promyelocytic leukemia (APL) results from a blockade of granulocyte differentiation at the promyelocytic stage. All-trans retinoic acid (ATRA) induces clinical remission in APL patients by enhancing the rapid differentiation of APL cells and the clearance of PML-RARα, APL's hallmark oncoprotein. In the present study, we demonstrated that both autophagy and Beclin 1, an autophagic protein, are upregulated during the course of ATRA-induced neutrophil/granulocyte differentiation of an APL-derived cell line named NB4 cells. This induction of autophagy is associated with downregulation of Bcl-2 and inhibition of mTOR activity. Small interfering RNA-mediated knockdown of BECN1 expression enhances apoptosis triggered by ATRA in NB4 cells but does not affect the differentiation process. These results provide evidence that the upregulation of Beclin 1 by ATRA constitutes an anti-apoptotic signal for maintaining the viability of mature APL cells, but has no crucial effect on the granulocytic differentiation. This finding may help to elucidate the mechanisms involved in ATRA resistance of APL patients, and in the ATRA syndrome caused by an accumulation of mature APL cells.

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