Sox4 is a key oncogenic target in C/EBPα mutant Acute Myeloid Leukemia

Details

• Alternative Title:
  Cancer Cell
• Personal Author:
  Zhang, Hong ; Alberich-Jordà, Meritxell ; Amabile, Giovanni ; Yang, Henry ; Staber, Philipp B. ; DiRuscio, Annalisa ; Welner, Rob ; Ebralidze, Alexander ; Zhang, Junyan ; Levantini, Elena ; Lefebvre, Véronique ; Valk, Peter J.M. ; Delwel, Ruud ; Hoogenkamp, Maarten ; Nerlov, Claus ; Cammenga, Jörg ; Saez, Borja ; Scadden, David T. ; Bonifer, Constanze ; Ye, Min ; Tenen, Daniel G.
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• Description:
  Mutation or epigenetic silencing of the transcription factor C/EBPα is observed in ∼10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBPα whereby its expression is inversely correlated with C/EBPα activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBPα mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBPα inactivation contributes to the development of leukemia with a distinct LIC phenotype.
• Subjects:
  • Article
  • Animals
  • CCAAT-Enhancer-Binding Proteins
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Gene Expression Regulation, Leukemic
  • Gene Knockdown Techniques
  • Hematopoietic Stem Cells
  • Humans
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• Source:
  Cancer Cell. 2013; 24(5):575-588
• Pubmed ID:
  24183681
• Pubmed Central ID:
  PMC4038627
• Document Type:
  Journal Article
• Funding:
  P01 CA066996/CA/NCI NIH HHSUnited States/ ; UL1 TR000439/TR/NCATS NIH HHSUnited States/ ; G0902418/MRC_/Medical Research CouncilUnited Kingdom/ ; R01 HL112719/HL/NHLBI NIH HHSUnited States/ ; K01 DP000086/DP/NCCDPHP CDC HHSUnited States/ ; R01 AR054153/AR/NIAMS NIH HHSUnited States/ ; R01 CA118316/CA/NCI NIH HHSUnited States/ ; CA118316/CA/NCI NIH HHSUnited States/ ; HL 56745/HL/NHLBI NIH HHSUnited States/ ; G0900892/MRC_/Medical Research CouncilUnited Kingdom/ ; R01 HL056745/HL/NHLBI NIH HHSUnited States/
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• Volume:
  24
• Issue:
  5
• Download URL:
  https://stacks.cdc.gov/view/cdc/41960/cdc_41960_DS1.pdf
• File Type:
  [PDF - 2.02 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:41bb23ee11dfa8a7a92ad4eba28e05df8119e310446ffb02d0e7d3482eaed184