title: Dissecting chronic lymphocytic leukemia microenvironment signals in patients with unmutated disease: microRNA-22 regulates phosphatase and tensin homolog/AKT/FOXO1 pathway in proliferative leukemic cells.
abstract: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells arrested in G0/G1 stages that coexist with proliferative B cells. We identified one of these proliferative subsets in the peripheral blood from patients with unmutated disease (UM). Aiming to characterize the molecular mechanism underlying this proliferative behavior, we performed gene expression analysis of the mRNA and microRNAs in this leukemic subpopulation and compared results with those for the quiescent counterpart. Our results suggest that proliferation of this subset mainly depends on microRNA-22 overexpression, which induces phosphatase and tensin homolog (PTEN) down-regulation and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. These results underline the role of the PI3K/AKT pathway at the origin of this proliferative pool in patients with UM CLL and provide additional rationale for the use of PI3K inhibitors.
authors.affiliation: Recombinant Protein Unit, Institut Pasteur de Montevideo , Uruguay.
authors.forename: Florencia
authors.initials: F
authors.lastname: Palacios
authors.forename: Daniel
authors.initials: D
authors.lastname: Prieto
authors.forename: Cecilia
authors.initials: C
authors.lastname: Abreu
authors.forename: Santiago
authors.initials: S
authors.lastname: Ruiz
authors.forename: Pablo
authors.initials: P
authors.lastname: Morande
authors.forename: Tamara
authors.initials: T
authors.lastname: Fernández-Calero
authors.forename: Gabriela
authors.initials: G
authors.lastname: Libisch
authors.forename: Ana Inés
authors.initials: AI
authors.lastname: Landoni
authors.forename: Pablo
authors.initials: P
authors.lastname: Oppezzo
mesh_terms: D019013:CD40 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016000:Cluster Analysis; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D000077022:Survivin; D059467:Transcriptome; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: C107489:BIRC5 protein, human; D019013:CD40 Antigens; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D051034:Inhibitor of Apoptosis Proteins; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D000077022:Survivin; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: CLL microenvironment signals; unmutated patients