The NOTCH1-MYC highway towards T-cell acute lymphoblastic leukemia.

Research paper by Marta M Sanchez-Martin, Adolfo A Ferrando

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: Blood


T cell acute lymphoblastic leukemia (T-ALL) is a highly proliferative hematologic malignancy resulting from the transformation of immature T-cell progenitors. Aberrant cell growth and proliferation in T-ALL lymphoblasts are sustained by activation of strong oncogenic drivers promoting cell anabolism and cell cycle progression. Oncogenic NOTCH signaling, which is activated in over 65% of T-ALL cases by activating mutations in the NOTCH1 gene, has emerged as a major regulator of leukemia cell growth and metabolism. T-ALL NOTCH1 mutations result in ligand independent and sustained NOTCH1 receptor signaling, which translate into activation of a broad transcriptional program dominated by upregulation of genes involved in anabolic pathways. Among these, the MYC oncogene plays a major role in NOTCH1 induced transformation. As result, the oncogenic activity of NOTCH1 in T-ALL is strictly dependent on MYC upregulation making the NOTCH1-MYC regulatory circuit an emerging attractive therapeutic target for the treatment of T-ALL.