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Role of SIRT1 in the growth and regulation of normal hematopoietic and leukemia stem cells

Li, Linga; Bhatia, Ravib

Current Opinion in Hematology: July 2015 - Volume 22 - Issue 4 - p 324–329
doi: 10.1097/MOH.0000000000000152
HEMATOPOIESIS: Edited by Hal E. Broxmeyer
Editor's Choice

Purpose of review Recent studies have enhanced our understanding of the role of the SIRT1 deacetylase in regulation of normal hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs), and its importance in regulating autophagy and epigenetic reprogramming in response to metabolic alterations.

Recent findings Studies employing conditional deletion mouse models indicate an important role of SIRT1 in maintenance of adult HSCs under conditions of stress. SIRT1 is significantly overexpressed in LSC populations from acute myeloid leukemia (AML) patients with the FLT3-ITD mutation, and maintains their survival, growth and drug resistance, as previously described for chronic myelogenous leukemia (CML). SIRT1 can also enhance leukemia evolution and drug resistance by promoting genetic instability. Recent studies indicate an important role of SIRT1 in regulating autophagy in response to oxidative stress and nutrient requirements, and have elucidated complex mechanisms by which SIRT1 regulates epigenetic reprogramming of stem cells.

Summary SIRT1 inhibition holds promise as a novel approach for ablation of LSCs in chronic phase CML or FLT3-ITD-associated AML. Additional studies to understand the role of SIRT1 in linking metabolic alterations to genomic stability, autophagy and epigenetic reprogramming of stem cells are warranted.

aDivision of Hematopoietic Stem Cell and Leukemia Research, City of Hope National Medical Center, Duarte, California

bDivision of Hematology–Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA

Correspondence to Ravi Bhatia, MD, Division of Hematology–Oncology, Department of Medicine, University of Alabama at Birmingham, 1802 6th Avenue, South, North Pavilion, Room 2555C, Birmingham, AL 35294, USA. Tel: +1 205 934 9591; e-mail: rbhatia@uabmc.edu

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