The canonical Notch signaling pathway is an evolutionary conserved pathway controlling the cell fate decisions, proliferation, development processes and stem cell maintenance. Notch1 plays an important but multifaceted role in several hematopoietic and solid malignancies. Chromosomal translocation and gain-of-function mutation of Notch1 gene is well known in T-ALL. Most of the mutation found is in HD and PEST domain in T-ALL. Mutational activation of the pathway leads to consistent transcription of target gene e.g. Hes1 and Hey1, driving progenitor proliferation.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western countries. CLL patients follow variable survival course, some with normal life expectancy without any therapy whereas others survive shorter than month despite aggressive therapy. Various deletion and point mutation are reported in the PEST domain of the Notch1 in CLL, which leads the truncation of protein and ablation of PEST domain. The PEST domain is responsible for the degradation of Notch through E3 ligase FBW7. Truncation of PEST domain prolongs the half-life of the NICD and activates Notch resulting in continuous cell proliferation and differentiation. Rare mutations are observed in Notch2.

To possibly identify mutation and copy number variation in the Notch1 and Notch2 genes in chronic lymphocytic leukemia (CLL) patient material and relate this to patient survival.