title: BCR-ABL promotes PTEN downregulation in chronic myeloid leukemia.
abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the t(9;22) translocation coding for the chimeric protein p210 BCR-ABL. The tumor suppressor PTEN plays a critical role in the pathogenesis of CML chronic phase, through non genomic loss of function mechanisms, such as protein down-regulation and impaired nuclear/cytoplasmic shuttling. Here we demonstrate that BCR-ABL promotes PTEN downregulation through a MEK dependent pathway. Furthermore, we describe a novel not recurrent N212D-PTEN point mutation found in the EM2 blast crisis cell line.
authors.affiliation: Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Panuzzo
authors.affiliation: Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Crivellaro
authors.affiliation: Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Carrà
authors.affiliation: Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Guerrasio
authors.affiliation: Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.affiliation: Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morotti
mesh_terms: D000818:Animals; D001752:Blast Crisis / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D041681:NIH 3T3 Cells; D051059:PTEN Phosphohydrolase / Q000378:metabolism*
chemical_list: D016044:Fusion Proteins, bcr-abl; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human