Familial chronic lymphocytic leukaemia: a survey and review of published studies

Abstract

B-cell chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia. To gain insight into the role of inherited factors in the disease, we have conducted a survey of the family histories of 268 CLL patients and have reviewed published familial cases and epidemiological studies. The results of our survey and published studies strongly support the hypothesis that a subset of the disease can be ascribed to a genetic predisposition. The most likely genetic model for inherited predisposition appears to be dominantly acting genes with pleiotropic effects because in many families CLL appears to be associated with other lymphoproliferative disorders.

Autoimmune conditions and chronic infections in chronic lymphocytic leukemia patients at diagnosis are associated with unmutated IgVH genes

“…Little is known about underlying factors or specific triggers, 1 although it seems clear that survival of CLL cells is associated with stimulation of and signaling through the Bcell receptor (BCR). 2 Leukemic cells are characterized by strikingly similar rearrangements of the immunoglobulin (Ig) variable region genes (IgVH) which are biased compared to normal B cells.…”

Genetic susceptibility to chronic lymphocytic leukemia

“…However, in a recent systematic survey of CLL, 6% of patients reported a family history of CLL and another 5% a family history of a LPD. 9 Published CLL pedigrees appear to be characterized by an earlier onset than sporadic forms of the disease, suggesting a more aggressive clonal expansion. One intriguing feature seen in the expression of CLL in many of the families reported is anticipation, the phenomenon of earlier onset and more severe phenotype in successive generations.…”

“…The established relationship between HLA and Hodgkin's 51 Sibs M, M Sib M LK Videbaek 1958 52 Uncle, nephew Hudson et al 1960 53 Sibs M, M; Sibs M, M Gunz et al 1962 54 Sibs F, M, M Fitzgerald et al 55 Furbetta et al 1963 56 Grandparent M, parent F, offspring F Wisniewski 1966 57 Parent M, offspring M Rigby 1966 58 2 half-sibs Ardizzone et al 1968 59 Sibs M, M Magaraggia et al 1968 60 Sibs M, M McPhedran et al 1969 61 Sibs F, M, F, cousins F, M, M Fraumeni et al; 62 Blattner et al 1969 63 Sibs F, M, M Gunz et al 1969 64 Sibs M, F Sib CGL Sibs M, M Undritz et al 1971 65 Sibs M, M, M, F Potolosky et al 1971 66 Sibs F, F Sib LY, sib LY, sib acute LK Schweitzer et al 1973 67 Sibs F, M, M, F, F Blattner et al; 68 Neuland et al; 69 Shen et al; 70 Parent M, offspring M, M, F, F Caporaso et al 1991 71 Gunz 1975 72 3 first degree; 3 others Petzholdt 1976 73 Sibs M, M, M Fazekas et al 1978 74 Sibs, M, M, M Branda et al 1978 75 Parent F; offspring M Conley et al 1980 76 Sibs F, F Sibs M, M Nephew, maternal aunt; Nephew M; greataunt Alfinito et al 1982 77 Sibs F, F Vanni et al 1983 78 Sibs F, F Brok-Simoni et al 79 MZ twins F, F, sib F Hakim et al 1987 80 Eriksson et al 1987 81 Sibs M, M; Sibs M, F; Sibs M, F; MZ twins M; Parent M, offspring M; Parent M, offspring M Shah et al 1992 82 Sibs F, M, F Cuttner 1993 83 Sibs M, M; Sib M NHL Parent M, offspring M; MZ twins M, M Fernhout et al 1997 84 Sibs F, F, F, F Yuille et al 2000 9 Parent …”

Chromosomal imbalances in familial chronic lymphocytic leukaemia: a comparative genomic hybridisation analysis

“…1 The aetiology of CLL is largely unknown, however, there is increasing evidence from epidemiological studies that a proportion of CLL has an inherited basis. 2 Family studies suggest that the most plausible genetic model for inherited predisposition is a dominantly acting gene with pleiotropic effects since, in some families, CLL co-exists with other lymphoproliferative disorders (LPD). 2 Most CLL families are small and so identification of predisposition genes through genome-wide linkage searches may be difficult, as the number of families required may be prohibitively large.…”

“…2 Family studies suggest that the most plausible genetic model for inherited predisposition is a dominantly acting gene with pleiotropic effects since, in some families, CLL co-exists with other lymphoproliferative disorders (LPD). 2 Most CLL families are small and so identification of predisposition genes through genome-wide linkage searches may be difficult, as the number of families required may be prohibitively large. A CLL susceptibility gene is likely to be a tumour suppressor and so an alternative strategy is to look for a region of recurrent genomic loss in tumour cells from familial cases.…”