miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia

Rosa Visone, Angelo Veronese, Laura Z. Rassenti, Veronica Balatti, Dennis K. Pearl, Mario Acunzo, Stefano Volinia, Cristian Taccioli, Thomas J. Kipps, Carlo M. Croce

Research output: Contribution to journalArticle

91 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3072-3079
Number of pages8
JournalBlood
Volume118
Issue number11
DOIs
StatePublished - Sep 15 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Visone, R., Veronese, A., Rassenti, L. Z., Balatti, V., Pearl, D. K., Acunzo, M., Volinia, S., Taccioli, C., Kipps, T. J., & Croce, C. M. (2011). miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia. Blood, 118(11), 3072-3079. https://doi.org/10.1182/blood-2011-01-333484