title: The NOTCH1-MYC highway toward T-cell acute lymphoblastic leukemia.
abstract: T-cell acute lymphoblastic leukemia (T-ALL) is a highly proliferative hematologic malignancy that results 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 more than 65% of T-ALL patients by activating mutations in theNOTCH1gene, has emerged as a major regulator of leukemia cell growth and metabolism. T-ALLNOTCH1mutations result in ligand-independent and sustained NOTCH1-receptor signaling, which translates into activation of a broad transcriptional program dominated by upregulation of genes involved in anabolic pathways. Among these, theMYConcogene plays a major role in NOTCH1-induced transformation. As result, the oncogenic activity of NOTCH1 in T-ALL is strictly dependent on MYC upregulation, which makes the NOTCH1-MYC regulatory circuit an attractive therapeutic target for the treatment of T-ALL.
authors.affiliation: Institute for Cancer Genetics.
authors.forename: Marta
authors.initials: M
authors.lastname: Sanchez-Martin
authors.affiliation: Institute for Cancer Genetics.|Department of Pathology, and.|Department of Pediatrics, Columbia University Medical Center, New York, NY.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Ferrando
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D051881:Receptor, Notch1