title: miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia.
abstract: MicroRNAs play a crucial role in chronic lymphocytic leukemia. We investigated whether microRNAs can discriminate patients with a progressive disease from patients with a stable disease. We analyzed microRNA expression on leukemic cells isolated from 358 sequential samples of 114 patients with either stable or progressive disease. We found that during the course of the disease the expression values of miR-181b, the most dysregulated microRNA, decreased in samples of patients with a progressive (P < .001, training and validation sets) but not in samples of patients with a stable disease (P = .3, training set; P = .2, validation set) over time. A drop of ≥ 50% between sequential samples and/or a miR-181b value ≤ 0.005 at the starting time point were significant to differentiate progressive from stable disease (P = .004, training set; P < .001, validation set). These parameters were associated with high risk of requiring treatment (risk ratio, 5.8; 95% confidence interval, 2.5-14.9). We also observed that miR-181b targets Mcl-1 protein and that the decrease of its expression inversely correlated with increased protein levels of MCL1 and BCL2 target genes. We conclude that parameters defined on the basis of the miR-181b expression values specify disease progression in chronic lymphocytic leukemia and are associated with clinical outcome.
authors.affiliation: Department of Molecular Virology, The Ohio State University, Columbus, OH, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Visone
authors.forename: Angelo
authors.initials: A
authors.lastname: Veronese
authors.forename: Laura Z
authors.initials: LZ
authors.lastname: Rassenti
authors.forename: Veronica
authors.initials: V
authors.lastname: Balatti
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Pearl
authors.forename: Mario
authors.initials: M
authors.lastname: Acunzo
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Cristian
authors.initials: C
authors.lastname: Taccioli
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015331:Cohort Studies; D018450:Disease Progression; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006367:HeLa Cells; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D046228:Microarray Analysis; D011379:Prognosis; D054928:Validation Studies as Topic
chemical_list: D014408:Biomarkers, Tumor; C540193:MIrn181 microRNA, human; D035683:MicroRNAs