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.
• 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:
  Animals Article CCAAT-Enhancer-Binding Proteins Cell Differentiation Cell Proliferation Cells, Cultured Gene Expression Regulation, Leukemic Gene Knockdown Techniques Hematopoietic Stem Cells Humans Leukemia, Myeloid, Acute Mice Mice, Knockout Mutation Myeloid Cells Neoplasm Transplantation Neoplastic Stem Cells Oncogenes SOXC Transcription Factors Transcriptome

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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/
• Volume:
  24
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:41bb23ee11dfa8a7a92ad4eba28e05df8119e310446ffb02d0e7d3482eaed184
• Download URL:
  https://stacks.cdc.gov/view/cdc/41960/cdc_41960_DS1.pdf
• File Type:
  [PDF - 2.02 MB ]