Notch 1 Mutation in Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma Patient

Chronic Lymphocytic Leukemia (CLL), is the most common leukemia in the western world. with a higher incidence in males (1.7:1),Current treatment strategies vary depending on disease burden, from active monitoring in asymptomatic patients, to targeted therapies in more advanced disease.

CLL is characterized by the clonal expansion of B cells with a characteristic immunophenotype (i.e., smIgweak, CD29+, CD23+, CD20weak) that slowly accumulate in peripheral blood, bone marrow, and lymphoid tissues mainly as a result of defects in the apoptosis machinery such as the overexpression of Bcl2 family anti-apoptotic proteins .

The clinical heterogeneity of CLL does reflect differences in the biology of the disease, particularly the IGHV mutational status and chromosomal alterations (i.e., del13q, del11q, trisomy 12 and del17p). Beside del17p/TP53 mutation which is the strongest CLL biomarker for response to therapy, other mutations (e.g., SF3B1, ATM, NOTCH1, BRIC3) have been reported to correlate with the outcome of the disease, but they are not actionable yet .

Non-Hodgins's lymphoma (NHL), the most common hematological malignancy worldwide, refers to a diverse class of B-cell and T-cell proliferations. NHL is differentiated from Hodgkin's lymphoma by different clinical characteristics and the absence of Reed-Sternberg cells and Cd15 and Cd30 staining on histology .

There are over 40 major subtypes, the most common types include indolent follicular lymphoma (FL) and aggressive diffuse large B-cell lymphoma (DLBCL). Each type is associated with unique driver genetic mutations (e.g., 14:18 translocation in FL, 11:14 translocation in Mantle Cell, 8:14 in Burkitts lymphoma ) and unique risk factors (Epstein-Barr Virus (EBV) for Burkitt's lymphoma, human T-cell lymphoma virus (HTLV-1) for T-cell lymphoma (de Leval et Jaffe,2020) The NOTCH gene was first named in studies of Drosophila melanogaster with notched wings in the 1910s, Homologs of NOTCH were then identified in multiple metazoans, and all these NOTCH homologs shared similar structures and signaling components.