Blood Journal
Leading the way in experimental and clinical research in hematology

The downregulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state

  1. Esmerina Tili1,
  2. Jean-Jacques Michaille2,
  3. Zhenghua Luo1,
  4. Stefano Volinia1,
  5. Laura Z. Rassenti3,
  6. Thomas J. Kipps3, and
  7. Carlo M. Croce1,*
  1. 1 Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, and Comprehensive Cancer Center, Columbus, OH, United States;
  2. 2 LBMN-INSERM U866, Universite de Bourgogne, Dijon, France;
  3. 3 CLL Research Consortium, Moores UCSD Cancer Center, San Diego, CA, United States
  1. * Corresponding author; email: carlo.croce{at}osumc.edu

Abstract

MiR-125b-1 maps at 11q24, a chromosomal region close to the epicenter of 11q23 deletions in chronic lymphocytic leukemias (CLLs). Our results establish that both aggressive and indolent CLL patients show reduced expression of miR-125b. Overexpression of miR-125b in CLL-derived cell lines resulted in the repression of many transcripts encoding enzymes implicated in cell metabolism. Metabolomics analyses showed that miR-125b overexpression modulated glucose, glutathione, lipid and glycerolipid metabolism. Changes on the same metabolic pathways were also observed in CLLs. We furthermore analyzed the expression of some of miR-125b-target transcripts that are potentially involved in the above metabolic pathways and defined a miR-125b-dependent CLL metabolism-related transcript signature. Thus, miR-125b acts as a master regulator for the adaptation of cell metabolism to a transformed state. MiR-125b and miR-125b-dependent metabolites therefore warrant further investigation as possible novel therapeutic approaches for CLLs.

  • Submitted March 8, 2012.
  • Accepted June 10, 2012.