Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic leukemia with high lipoprotein lipase expression.
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.
Bilban
M
M
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Heintel
D
D
Scharl
T
T
Woelfel
T
T
Auer
M M
MM
Porpaczy
E
E
Kainz
B
B
Kröber
A
A
Carey
V J
VJ
Shehata
M
M
Zielinski
C
C
Pickl
W
W
Stilgenbauer
S
S
Gaiger
A
A
Wagner
O
O
Jäger
U
U
D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics; D016189:Dystrophin / Q000235:genetics; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058112:Septins
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D005227:Fatty Acids; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D008071:Lipoprotein Lipase; D020558:GTP Phosphohydrolases; C474375:SEPTIN10 protein, human; D058112:Septins