Insight into the pathogenesis of chronic lymphocytic leukemia (CLL) through analysis of IgVH gene usage and mutation status in familial CLL.
To address the proposition that familial B-cell chronic lymphocytic leukemia (CLL) may exhibit a more restricted phenotype than sporadic CLL with respect to immunoglobulin gene usage or ontogenic development, we compared immunoglobulin (Ig) heavy chain variable region (VH) gene usage and IgVH mutation status in 327 patients with CLL from 214 families with 724 patients with sporadic cases. The frequency of mutated CLL was higher in familial CLL (P < .001), and there was evidence of intrafamilial concordance in mutation status (P < .001). The repertoire and frequency of IgVH usage was, however, not significantly different between familial and sporadic CLL. Furthermore, IgVH usage was not correlated between affected members of the same family. These observations provide evidence that familial CLL is essentially indistinguishable from sporadic CLL, favoring a genetic basis to disease development in general rather than a simple environmental etiology.
Crowther-Swanepoel
Dalemari
D
Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom.
Wild
Ruth
R
Sellick
Gabrielle
G
Dyer
Martin J S
MJ
Mauro
Francesca R
FR
Cuthbert
Robert J G
RJ
Jonsson
Viggo
V
Matutes
Estella
E
Dearden
Claire
C
Wiley
James
J
Fuller
Stephen
S
Catovsky
Daniel
D
Houlston
Richard S
RS
D004777:Environment; D005192:Family Health; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology* / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region