title: Insight into the pathogenesis of chronic lymphocytic leukemia (CLL) through analysis of IgVH gene usage and mutation status in familial CLL.
abstract: 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.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Dalemari
authors.initials: D
authors.lastname: Crowther-Swanepoel
authors.forename: Ruth
authors.initials: R
authors.lastname: Wild
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Sellick
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Mauro
authors.forename: Robert J G
authors.initials: RJ
authors.lastname: Cuthbert
authors.forename: Viggo
authors.initials: V
authors.lastname: Jonsson
authors.forename: Estella
authors.initials: E
authors.lastname: Matutes
authors.forename: Claire
authors.initials: C
authors.lastname: Dearden
authors.forename: James
authors.initials: J
authors.lastname: Wiley
authors.forename: Stephen
authors.initials: S
authors.lastname: Fuller
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: 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
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region