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 V-H 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. V H gene analysis demonstrated clonal rearrangements of the V(H)3 gene family in 5 cases and of V(H)2 genes in I case. All 6 cases were mutated in V(H)2 or V(H)3. Two cases had a second V H I 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.