Document Type
Journal Article
Keywords
acyl coenzyme A desaturase 1, BCR ABL protein, CD45 antigen, mammalian target of rapamycin, peroxisome proliferator activated receptor gamma agonist, phosphatidylinositol 3 kinase, phosphatidylinositol 3, 4, 5 trisphosphate 3 phosphatase, protein bcl 2, protein kinase B, protein p53, animal cell, animal experiment, animal model, apoptosis, article, cancer inhibition, cancer stem cell, cancer survival, cell survival, chronic myeloid leukemia, controlled study, down regulation, gene control, gene deletion, gene induction, gene overexpression, hematopoietic stem cell, human, human cell, leukemia cell, leukemogenesis, mouse, nonhuman, nucleotide sequence, priority journal, protein expression, 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
Publisher
American Society for Microbiology
Faculty
Faculty of Computing, Health and Science
School
School of Computer and Security Science
RAS ID
15297
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.
Access Rights
free_to_read
Comments
This is an Author's Accepted Manuscript of: Zhang, H., Li, H., Ho, N., Li, D. , & Li, S. (2012). Scd1 plays a tumor-suppressive role in survival of leukemia stem cells and the development of chronic myeloid leukemia. Molecular and Cellular Biology, 32(10), 1776-1787. Available here