Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic leukemia with high lipoprotein lipase expression

Leukemia. 2006 Jun;20(6):1080-8. doi: 10.1038/sj.leu.2404220.


Lipoprotein lipase (LPL) is a prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL) related to immunoglobulin V(H) gene (IgV(H))mutational status. We determined gene expression profiles using Affymetrix U133A GeneChips in two groups of B-CLLs selected for either high ('LPL+', n=10) or low ('LPL-', n=10) LPL mRNA expression. Selected genes were verified by real-time PCR in an extended patient cohort (n=42). A total of 111 genes discriminated LPL+ from LPL- B-CLLs. Of these, the top three genes associated with time to first treatment were Septin10, DMD and Gravin (P</=0.01). The relationship of LPL+ and LPL- B-CLL gene expression signatures to 52 tissues was statistically analyzed. The LPL+ B-CLL expression signature, represented by 64 genes was significantly related to fat, muscle and PB dendritic cells (P<0.001). Exploration of microarray data to define functional alterations related to the biology of LPL+ CLL identified two functional modules, fatty acid degradation and MTA3 signaling, as being altered with higher statistical significance. Our data show that LPL+ B-CLL cells have not only acquired gene expression changes in fat and muscle-associated genes but also in functional pathways related to fatty acid degradation and signaling which may ultimately influence CLL biology and clinical outcome.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Cytoskeletal Proteins / genetics
  • Dystrophin / genetics
  • Fatty Acids / genetics
  • Fatty Acids / metabolism
  • GTP Phosphohydrolases / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Variable Region / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Lipoprotein Lipase / biosynthesis
  • Lipoprotein Lipase / genetics*
  • Mutation
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Septins


  • Cytoskeletal Proteins
  • Dystrophin
  • Fatty Acids
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • RNA, Messenger
  • Lipoprotein Lipase
  • GTP Phosphohydrolases
  • SEPTIN10 protein, human
  • Septins