Four aged siblings with B cell chronic lymphocytic leukemia

Abstract

All four aged siblings (Ͼ80 years) of one family presented with B cell chronic lymphocytic leukemia (B-CLL). In an attempt to find common characteristics in the four patients, we performed detailed immunological marker analysis, Southern blot analysis of immunoglobulin (Ig) genes, and cytogenetic studies. In three patients clonality of the B-cells could be proven by single Ig light chain expression, but in the fourth patient no Ig light chain expression was detected and clonality of the B cells could only be demonstrated by Southern blot analysis of the Ig genes. Interestingly, in two patients, the Ig gene rearrangement patterns were compatible with the presence of two independent B cell clones, whereas in the two other siblings a monoclonal rearrangement pattern was found. All four patients showed clonal chromosome aberrations, which were different in each patient. In the two patients with biclonal Ig gene rearrangement patterns, two unrelated clones could also be demonstrated by the cytogenetic studies. These combined Ig gene and cytogenetic data indicate the presence of two different B-CLL in two of the four patients. Remarkably, the B-CLL cells of the two oldest patients expressed the CD8 antigen, which is rarely observed. Our finding of six different B-CLL in the four living siblings indicates that the members of this family are highly susceptible to the development of B-CLL. However we could not identify a common factor to explain this susceptibility further. In contrast to the literature, the occurrence of two B-CLL in one patient and the expression of CD8 were not associated with clinically aggressive disease in this family.

Anticipation in familial chronic lymphocytic leukaemia

“…Over 70 pedigrees have been reported (most recently last year 11 ) over the last seven decades describing the clustering in families of CLL and, sometimes, other lymphoproliferative disorders. Although early reports on familial CLL were described before B cells had been described, most of the diagnoses are likely to be accurate since diagnosis of CLL may be distinguished from other leukaemias on clinical and morphological grounds.…”

Hereditary chronic lymphocytic leukemia: An extended family study and literature review

“…Hereditary factors appear to be a major contributing determinant in a subset of CLL cases. Several studies have shown evidence of familial clustering of CLL in siblings [Cartwright et al, 1987; Shah et al, 1992; Fernhout et al, 1997]. One study also reported evidence of familial CLL in association with breast cancer [Linet et al, 1989].…”

“…One study also reported evidence of familial CLL in association with breast cancer [Linet et al, 1989]. Shah et al [1992] reported the cases of three of six siblings in whom CLL developed at ages 64, 67, and 68 years, while Fernhout et al [1997] described the cases of four siblings more than 80 years of age with CLL. All four of the latter siblings showed clonal chromosome aberrations, which were different in each patient.…”

Genetic susceptibility to chronic lymphocytic leukemia

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