title: Proteostasis alterations in myeloproliferative neoplasms: Oncogenic relevance and therapeutic opportunities.
abstract: Myeloproliferative neoplasms (MPNs) represent a frequently occurring group of heterogeneous hematologic malignancies. In the last decade, the identification of JAK2-activating mutations in a significant proportion of MPN patients gave rise to the first molecularly driven therapy for BCR-ABL-negative patients. Nevertheless, current efforts are still focused on the identification of novel therapeutic targets to achieve permanent remission. In this perspective, we focus on the recent findings in this field and highlight new evidence linking proteostasis deregulation with myeloid transformation. We recently reported that the proteostasis regulator AIRAPL acts as a tumor suppressor in MPNs through the modulation of insulin-like growth factor receptor levels at the endoplasmic reticulum. This finding paves the way for new therapeutic approaches to these neoplasms and indicates the importance of protein homeostasis maintenance for normal hematopoiesis.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain.
authors.forename: Olaya
authors.initials: O
authors.lastname: Santiago-Fernández
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain.
authors.forename: Fernando G
authors.initials: FG
authors.lastname: Osorio
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain. Electronic address: clo@uniovi.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D057165:Proteostasis Deficiencies / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C544166:ZFAND2B protein, human