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Scd1 plays a tumor-suppressive role in survival of leukemia stem cells and the development of chronic myeloid leukemia.

Abstract

Chronic myeloid leukemia (CML) is derived from a stem cell, and it is widely accepted that the existence of leukemia stem cells (LSCs) is one of the major reasons for the relapse of CML treated with kinase inhibitors. Key to eradicating LSCs is to identify genes that play a critical role in survival regulation of these stem cells. Using BCR-ABL-induced CML mouse model, here we show that expression of the stearoyl-CoA desaturase 1 (Scd1) gene is downregulated in LSCs and that Scd1 plays a tumor-suppressive role in LSCs with no effect on the function of normal hematopoietic stem cells. Deletion of Scd1 causes acceleration of CML development and conversely overexpression of Scd1 delays CML development. In addition, using genetic approaches, we show that Pten, p53, and Bcl2 are regulated by Scd1 in LSCs. Furthermore, we find that induction of Scd1 expression by a PPARγ agonist suppresses LSCs and delays CML development. Our results demonstrate a critical role for Scd1 in functional regulation of LSCs, providing a new anti-LSC strategy through enhancing Scd1 activity.

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  • Authors

    Zhang H, Li H, Ho N, Li D, Li S

    Institution

    Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

    Source

    Molecular and cellular biology 32:10 2012 May pg 1776-87

    MeSH

    Animals
    Down-Regulation
    Fusion Proteins, bcr-abl
    Gene Expression Regulation, Neoplastic
    Genes, Tumor Suppressor
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Mice
    Neoplastic Stem Cells
    PPAR gamma
    Stearoyl-CoA Desaturase

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22431519