Linkage analysis for major histocompatibility complex-related genetic susceptibility in familial chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis is poorly understood. The existence of a linkage betw een HLA and Hodgkin lymphoma, another B-cell disorder, coupled with the fac t that CLL is frequently associated with autoimmune disease, led to the que stion of whether the major histocompatibility complex (MHC) region is invol ved in familiar cases of CLL. To examine this proposition, 5 microsatellite markers on chromosome 6p21.3 were typed in 28 families with CLL, 4 familie s with CLL in association with other lymphoproliferative disorders, and 1 f amily with splenic lymphoma with villous lymphocytes. There was no evidence of linkage in these families to chromosome 6p21.3. The best estimates of t he proportions of sibling pairs with CLL that share 0, 1, or 2 MHC haplotyp es were not significantly different from the null expectation. This implies that genes within the MHC region are unlikely to be the major determinants of familiar CLL. (C) 2000 by The American Society of Hematology.