Familial B-cell chronic lymphocytic leukemia: analysis of cytogenetic abnormalities, immunophenotypic profiles, and immunoglobulin heavy chain gene usage.
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.
Aoun
Patricia
P
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
Zhou
Guimei
G
Chan
Wing C
WC
Page
Cynthia
C
Neth
Kellie
K
Pickering
Diane
D
Sanger
Warren
W
Quinn-Laquer
Brigid
B
Watson
Patrice
P
Lynch
Jane F
JF
Lynch
Henry T
HT
Weisenburger
Dennis D
DD
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
D007143:Immunoglobulin Heavy Chains