Thrombocytopenia-associated mutations in the ANKRD26 regulatory region induce MAPK hyperactivation

• Published in: The Journal of clinical investigation Vol. 124; no. 2; pp. 580 - 591
• Main Authors: Bluteau, Dominique, Balduini, Alessandra, Balayn, Nathalie, Currao, Manuela, Nurden, Paquita, Deswarte, Caroline, Leverger, Guy, Noris, Patrizia, Perrotta, Silverio, Solary, Eric, Vainchenker, William, Debili, Najet, Favier, Remi, Raslova, Hana
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.02.2014
• Subjects: 5' Untranslated Regions; Adolescent; Adult; Base Sequence; Binding Sites; Biomedical research; Cell Differentiation; Cellular signal transduction; Chromosome Breakage; Chromosome Disorders - genetics; Core Binding Factor Alpha 2 Subunit - metabolism; Defects; Development and progression; Enzyme Activation; Extracellular signal-regulated kinases; Female; Gene expression; Gene Expression Regulation; Gene mutations; Gene Silencing; Genetic aspects; Human health and pathology; Humans; Infant; Intercellular Signaling Peptides and Proteins; Leukemia; Life Sciences; Male; MAP Kinase Signaling System; Megakaryocytes - cytology; Middle Aged; Molecular Sequence Data; Mutation; Nuclear Proteins - genetics; Patients; Pedigree; Proteins; Proto-Oncogene Protein c-fli-1 - metabolism; Receptors, Thrombopoietin - metabolism; Scholarships & fellowships; Signal Transduction; Thrombocytopenia; Thrombocytopenia - congenital; Thrombocytopenia - genetics; Transcription factors; Young Adult

Point mutations in the 5' UTR of ankyrin repeat domain 26 (ANKRD26) are associated with familial thrombocytopenia 2 (THC2) and a predisposition to leukemia. Here, we identified underlying mechanisms of ANKRD26-associated thrombocytopenia. Using megakaryocytes (MK) isolated from THC2 patients an...