Notch is oncogenic dominant in T-cell acute lymphoblastic leukemia

Renée M. Demarest, Nadia Dahmane, Anthony J. Capobianco

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic neoplasm characterized by malignant expansion of immature T cells. Activated NOTCH (NotchIC) and c-MYC expression are increased in a large percentage of human T-ALL tumors. Furthermore, c-MYC has been shown to be a NOTCH target gene. Although activating mutations of Notch have been found in human T-ALL tumors, there is little evidence that the c-MYC locus is altered in this neoplasm. It was previously demonstrated that Notch and c-Myc-regulated genes have a broadly overlapping profile, including genes involved in cell cycle progression and metabolism. Given that Notch and c-Myc appear to function similarly in T-ALL, we sought to determine whether these two oncogenes could substitute for each other in T-ALL tumors. Here we report that NOTCH IC is able to maintain T-ALL tumors formed in the presence of exogenous NOTCHIC and c-MYC when exogenous c-MYC expression is extinguished. In contrast, c-MYC is incapable of maintaining these tumors in the absence of NOTCHIC. We propose that failure of c-MYC to maintain these tumors is the result of p53-mediated apoptosis. These results demonstrate that T-ALL maintenance is dependent on NOTCHIC, but not c-MYC, demonstrating that NOTCH is oncogenic dominant in T-ALL tumors.

Original languageEnglish (US)
Pages (from-to)2901-2909
Number of pages9
JournalBlood
Volume117
Issue number10
DOIs
StatePublished - Mar 10 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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