title: From mRNA metabolism to cancer therapy: chronic myelogenous leukemia shows the way.
abstract: Altered mRNA metabolism is a feature of many cancers including blast crisis chronic myelogenous leukemia. Indeed, loss of function of many tumor suppressors regulating cell proliferation, survival, and differentiation results from aberrant mRNA processing, nuclear export, and/or translation. Here, we summarize the effects of increased BCR/ABL oncogenic activity on the expression and function of RNA binding proteins (e.g., FUS, hnRNP A1, hnRNP E2, hnRNP K, and La/SSB) with posttranscriptional and translational regulatory activities and their importance for the phenotype of BCR/ABL-transformed hematopoietic progenitors. We also provide evidence that these studies not only advance our understanding on the molecular mechanisms contributing to tumor/leukemia emergence, maintenance, and/or progression but they also serve for the identification of novel molecular targets useful for the development of alternative therapies for imatinib-resistant and blast crisis chronic myelogenous leukemia and, perhaps, for other cancers characterized by similar alterations in the mRNA metabolism.
authors.affiliation: The Molecular Biology and Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43240, USA. danilo.perrotti@osumc.edu
authors.forename: Danilo
authors.initials: D
authors.lastname: Perrotti
authors.forename: Paolo
authors.initials: P
authors.lastname: Neviani
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000502:physiology; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology; D000067879:CELF1 Protein; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology; D004268:DNA-Binding Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000502:physiology; D056488:Histone Chaperones; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000628:therapy*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D010446:Peptide Fragments / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology; D012261:Ribonucleoproteins / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology
chemical_list: D001324:Autoantigens; D022762:CCAAT-Enhancer-Binding Proteins; D000067879:CELF1 Protein; C102843:CELF1 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D056488:Histone Chaperones; C506261:SSB protein, human; D010446:Peptide Fragments; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D012261:Ribonucleoproteins; C513473:SET protein, human; D014157:Transcription Factors; C072074:HNRNPK protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D010749:Phosphoprotein Phosphatases