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  • Zhang, Hong, et al. (author)
  • Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia
  • 2013
  • In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 24:5, s. 575-588
  • Journal article (peer-reviewed)abstract
    • Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 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/EBP alpha whereby its expression is inversely correlated with C/EBP alpha 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/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype.
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