In:
Blood, American Society of Hematology, Vol. 92, No. 10 ( 1998-11-15), p. 3772-3779
Abstract:
B-cell chronic lymphocytic leukemia (B-CLL) and autoimmune disease are a related event, and genetic factors are linked to both diseases. As B-CLL is mainly of B-1 cell type that participates in autoantibody production, genetically-determined regulatory abnormalities in proliferation and/or differentiation of B-1 cells may determine their fate. We earlier found that, in H-2–congenic (NZB × NZW) F1 mice, while H-2d/z heterozygosity predisposes to autoimmune disease, H-2z/z homozygosity predisposes to B-CLL. Studies also suggested the involvement of non–H-2-linked NZW allele(s) in leukemogenesis. Using H-2–congenic NZW and B10 mouse strains, their F1 and backcross progeny, we have now identified three major NZW susceptibility loci for abnormal proliferation of B-1 cells, which form the basis of leukemogenesis; one H-2–linked locus on chromosome 17 and the other two non–H-2-linked loci, each on chromosome 13 and chromosome 17. Each susceptibility allele functioned independently, in an incomplete dominant fashion, the sum of effects determining the extent of aberrant B-1 cell frequencies. The development of leukemia was associated with age-related increase in B-1 cell frequencies in the blood. Thus, these alleles probably predispose B-1 cells to accumulate genetic alterations, giving rise to B-CLL. Potentially important candidate genes and correlation of the findings with autoimmune disease are discussed.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood.V92.10.3772
Language:
English
Publisher:
American Society of Hematology
Publication Date:
1998
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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