title: Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients.
abstract: Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL) as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML.
authors.affiliation: Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Lyon, France.|Université Lyon 1, Lyon, France.|Nuclear domains and pathologies team, Cancer Cell Plasticity Department, Lyon, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Marcel
authors.affiliation: Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Lyon, France.|Université Lyon 1, Lyon, France.|Nuclear domains and pathologies team, Cancer Cell Plasticity Department, Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Catez
authors.affiliation: Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Lyon, France.|Université Lyon 1, Lyon, France.|Nuclear domains and pathologies team, Cancer Cell Plasticity Department, Lyon, France.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Berger
authors.affiliation: Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Lyon, France.|Université Lyon 1, Lyon, France.|Anticancer antibodies team, Immunity, Microenvironment and Virus Department, Lyon, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Perrial
authors.affiliation: Department of Biology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Adriana
authors.initials: A
authors.lastname: Plesa
authors.affiliation: Department of Hematology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.affiliation: Department of Biology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Eve
authors.initials: E
authors.lastname: Mattei
authors.affiliation: Department of Biology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Hayette
authors.affiliation: Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Lyon, France.|Université Lyon 1, Lyon, France.|Department of Medecine, Centre Léon Bérard, Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Saintigny
authors.affiliation: Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Lyon, France.|Université Lyon 1, Lyon, France.|Nuclear domains and pathologies team, Cancer Cell Plasticity Department, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouvet
authors.affiliation: Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Lyon, France.|Université Lyon 1, Lyon, France.|Nuclear domains and pathologies team, Cancer Cell Plasticity Department, Lyon, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Diaz
authors.affiliation: Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Lyon, France.|Université Lyon 1, Lyon, France.|Anticancer antibodies team, Immunity, Microenvironment and Virus Department, Lyon, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult; D000097796:Nucleolin
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C486600:NOP56 protein, human