NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth

The NOTCH1 signaling pathway directly links extracellular signals with transcriptional responses in the cell nucleus and plays a critical role during T cell development and in the pathogenesis over 50% of human T cell lymphoblastic leukemia (T-ALL) cases. However, little is known about the transcriptional programs activated by NOTCH1. Using an integrative systems biology approach we show that NOTCH1 controls a feed-forward-loop transcriptional network that promotes cell growth. Inhibition of NOTCH1 signaling in T-ALL cells led to a reduction in cell size and elicited a gene expression signature dominated by down-regulated biosynthetic pathway genes. By integrating gene expression array and ChIP-on-chip data,…

• EU
  Elsa U. Pardee Foundation
• GA
  Golfers Against Cancer
• NI
  National Institutes of Health

  Awards: 1U54CA121852-01A1, LM007079, T15 LM007079
• NC
  National Cancer Institute
• NI
  National Institute of Allergy and Infectious Diseases
• UN
  U.S. National Library of Medicine

  Award: T15 LM007079