title: Familial B-cell chronic lymphocytic leukemia: analysis of cytogenetic abnormalities, immunophenotypic profiles, and immunoglobulin heavy chain gene usage.
abstract: B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease that may exhibit familial clustering. We examined the cytogenetic, immunophenotypic, and VH gene usage characteristics of a family with B-CLL affecting 7 members in 3 generations. Interphase fluorescence in situ hybridization studies identified an acquired deletion of chromosome 13q14 in the leukemic cells of 6 affected members, accompanied by deletion 14q32 or trisomy 12 in 2 cases. VH gene analysis demonstrated clonal rearrangements of the VH3 gene family in 5 cases and of VH2 genes in 1 case. All 6 cases were mutated in VH2 or VH3. Two cases had a second VH1 family gene rearrangement that was unmutated. Flow cytometry performed on 5 cases showed the typical B-CLL immunophenotype; all were CD38-, but 3 expressed ZAP-70. Our findings support previous observations that familial and sporadic B-CLL cases are biologically similar and suggest that familial clusters will be useful for studying pathogenetic events in B-CLL.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aoun
authors.forename: Guimei
authors.initials: G
authors.lastname: Zhou
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Cynthia
authors.initials: C
authors.lastname: Page
authors.forename: Kellie
authors.initials: K
authors.lastname: Neth
authors.forename: Diane
authors.initials: D
authors.lastname: Pickering
authors.forename: Warren
authors.initials: W
authors.lastname: Sanger
authors.forename: Brigid
authors.initials: B
authors.lastname: Quinn-Laquer
authors.forename: Patrice
authors.initials: P
authors.lastname: Watson
authors.forename: Jane F
authors.initials: JF
authors.lastname: Lynch
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D005192:Family Health; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D007143:Immunoglobulin Heavy Chains