Preferred usage of specific immunoglobulin gene segments in chronic lymphocytic leukaemia cells of three HLA‐identical sisters

Abstract

We report three family members, including a set of identical twins, who developed CD5 positive B-CLL. The patients are female Ashkenazi Jews sharing an identical HLA phenotype. Two of the HLA loci (B35 and Cw4) were common with those already described as being shared by Ashkenazi Jews with an increased incidence of CLL. The rearranged immunoglobulin genes of the malignant cells of all three patients were found to express genetically related VH regions belonging to the VH3 subgroup, and chromosomal studies suggest a process of clonal evolution in one of the twins.

VH gene usage by family members affected with chronic lymphocytic leukaemia

“…Following a pattern reported in two previous isolated descriptions of familial CLL ( Shen et al , 1987 ; Hakim et al , 1995 ), initial data obtained from the four French families suggested that within a family affected members tended to express V H gene segments that belonged to the same clan (clan I for families 9 and 10, clan II and III respectively for families 11 and 12), raising the possibility that one or more superantigens might play a role in the development of the disease ( Troussard et al , 1996 ). However, extension of the analysis to eight new families from Italy demonstrated clan identity in only two of the eight families (families 3 and 8).…”

“…Among unrelated patients, expression of V H families is close to the complexity of the system (Table III). Initial reports of V H gene usage among an American and an Israeli family suggested a restriction in clan usage among members of a given family affected by CLL that was compatible with selection by a superantigen (Shen et al, 1987;Hakim et al, 1995). An initial study of four French families revealed a similar restriction in V H clan utilization that was supportive of this hypothesis (Troussard et al, 1996).…”

Increased sex concordance of sibling pairs with chronic lymphocytic leukemia

“…7 Furthermore, preferred usage of specific IG gene segments has been reported in three sisters affected with CLL. 8 Whatever the biological basis of familial CLL our findings suggest that aggregation of the disease in families is due, in part, to interactions between both environmental risk factors and inherited genetic susceptibility. The paucity of affected spouse pairs relative to sibling pairs with CLL in the literature provides some evidence that aggregation of disease occurs primarily on a background of genetic susceptibility.…”

Genetic susceptibility to chronic lymphocytic leukemia

“…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 …”