MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia

Our experiments demonstrate that miR-650 expression is regulated by coupled expression with its host gene for IgLλ

Marek Mraz

2012

Scholarcy highlights

  • Chronic lymphocytic leukemia originates from antigen experienced B-cells, and its biology is largely influenced by antigen stimulation, immunoglobulin structure, and BCR-signaling
  • Our group and others have previously described the role of miRNAs in CLL pathogenesis, prognosis, and progression
  • We analyzed the miR-650 expression and the exact variable segment used by CLL cells in 47 patients
  • The monoclonal nature of CLL enabled us to demonstrate that miR-650 expression is likely naturally activated by the promoter for IgLλ and is coupled with the expression of its V2 family members
  • The multivariate analysis by Cox proportional hazards model demonstrated that higher expression of miR-650 is a significant independent predictor of survival and time to first treatment
  • This observation is surprising because previously published data suggested that miR-650 is expressed independently of immunoglobulin genes
  • early B-cell factor 3 is a member of the “Early B-cell Factor” family, which is recognized as an important transcription regulator of survival and development of B-lineage cells.24 The transfection of B cells with miR-650 resulted in down-regulation of protein levels of cyclin dependent kinase 1, inhibitor of growth 4, and EBF3 by 53%, 64%, and 67%, respectively

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