1. The Role of Notch1 signaling in T-cell acute lymphoblastic leukemia

2. T-ALL accounts for 10% to 15% of pediatric and 25% of adult acute lymphoblastic leukemia cases.

3. The Notch 1 receptor functions as a ligand activated transcription factor that transduces EC signals into changes in gene expression

4. Activated NOTCH1 receptors occurs via cell-cell contact and interaction with Delta-like or Jagged ligand expressed on the surface of a neighboring cell
Cold Spring Harb Perspect Biol 2012;4:a011213

5. Induced inactivation of Notch1 in newborn mice resulted in growth retardation and abnormal T-cell development

6. In the hematopoietic system NOTCH1 activation plays a critical role at multiple stages of T-Cell development

7. Constitutive activation of Notch1 was first observed in rare leukemia cases containing t(7;9) translocation

8. More than 50% of human T-ALLs have activating mutations that involve HD domain and/or the C-terminal PEST domain of Notch1

9. Mutations in the HD and PEST domain are divided into four classes/groups

10. GSI treatment of T-ALL cell lines harboring activating mutations in NOTCH1 induce rapid clearance of intracellular activated NOTCH1

11. Works Cited
Aster JC, Pear WS, Blacklow SC. Notch Signaling in Leukemia. Annu Rev Pathol 2008;3:587–613.[PubMed: ]
Tanigaki K, Honjo T. Regulation of lymphocyte development by Notch signaling. Nat Immunol. 2007;8:451–456. [PubMed: ]
Weng AP, Ferrando AA, Lee W, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004;306:269–271. [PubMed: ]
Yuan, Xun et al. Notch Signalling