Unique gene expression and clinical characteristics are associated with the 11q23 deletion in chronic lymphocytic leukaemia.
Chromosome abnormalities influence prognosis and tumour progression in B-cell Chronic Lymphocytic Leukaemia (CLL). This study sought to determine whether these different disease subgroups were associated with unique gene expression patterns. Thirty-four cases of CLL were screened for the 11q23, 13q14, 17p13 deletions, and trisomy 12 by fluorescence in situ hybridization (FISH). Expression of 205 cell signalling and apoptosis genes were compared by cDNA array among cases with different chromosome abnormalities. A majority of the statistically differentially expressed genes were present in the 11q23 deletion group by hierarchical clustering. CDC2, a serine/threonine kinase, was overexpressed in the 11q23 deletion group (P = 0.0004) and confirmed by Taqman real-time polymerase chain reaction. Several other genes associated with cell signalling were overexpressed in the 11q23 deletion group. A strong overall correlation existed between the presence of different chromosome abnormalities and a number of prognostic factors including immunoglobulin heavy chain variable region mutation status (P = 0.011), time to treatment (P = 0.025) and lymphocyte doubling time (P = 0.034). This study confirmed the prognostic impact of chromosome abnormalities identified by FISH in CLL, particularly the 11q23 deletion and trisomy 12. In addition, the 11q23 deletion group was associated with a unique gene expression pattern involving cell signalling and apoptosis genes.
Dickinson
John D
JD
Department of Genetics, Cell Biology, & Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-6395, USA.
Smith
Lynette M
LM
Sanger
Warren G
WG
Zhou
Guimei
G
Townley
Peter
P
Lynch
James C
JC
Pavletic
Z Steven
ZS
Bierman
Philip J
PJ
Joshi
Shantaram S
SS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region