title: The non-genomic loss of function of tumor suppressors: an essential role in the pathogenesis of chronic myeloid leukemia chronic phase.
abstract: Chronic Myeloid Leukemia was always referred as a unique cancer due to the apparent independence from tumor suppressors' deletions/mutations in the early stages of the disease. However, it is now well documented that even genetically wild-type tumor suppressors can be involved in tumorigenesis, when functionally inactivated. In particular, tumor suppressors' functions can be impaired by subtle variations of protein levels, changes in cellular compartmentalization and post-transcriptional/post-translational modifications, such as phosphorylation, acetylation, ubiquitination and sumoylation. Notably, tumor suppressors inactivation offers challenging therapeutic opportunities. The reactivation of an inactive and genetically wild-type tumor suppressor could indeed promote selective apoptosis of cancer cells without affecting normal cells.
  
  
  
  Chronic Myeloid Leukemia (CML) could be considered as the paradigm for non-genomic loss of function of tumor suppressors due to the ability of BCR-ABL to directly promote functionally inactivation of several tumor suppressors.
  
  
  
  In this review we will describe new insights on the role of FoxO, PP2A, p27, BLK, PTEN and other tumor suppressors in CML pathogenesis. Finally, we will describe strategies to promote tumor suppressors reactivation in CML.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Crivellaro
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Carrà
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Panuzzo
authors.affiliation: Department of Oncology, University of Turin, Orbassano, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Taulli
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Guerrasio
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Italy. alessandro.morotti@unito.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morotti
mesh_terms: D000818:Animals; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D015894:Genome, Human; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins
keywords: Chronic myeloid leukemia; Non genomic loss of function; Tumor suppressor; Tyrosine kinase inhibitors