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Differential rates of somatic hypermutation in V(H) genes among subsets of
chronic lymphocytic leukemia defined by chromosomal abnormalities
DG Oscier, A Thompsett, D Zhu and FK Stevenson
Department of Haematology, Royal Bournemouth Hospital, UK.
Chronic lymphocytic leukemia (CLL) is a B-cell tumor involving small
lymphocytes that generally express the CD5 antigen and low levels of
surface Ig. Within this definition, there is heterogeneity among cases in
cell morphology, karyotypic abnormalities, and clinical course. Trisomy 12,
the most frequent karyotypic abnormality, is commonly found in a subset of
CLL with atypical morphology. It has also been associated with advanced
disease, and possibly with a less favorable prognosis. A further subset of
cases with abnormalities involving chromosome 13q14 have typical lymphocyte
morphology. Occasionally, the two abnormalities are found together. To
assess the clonal history of the cell of origin in disease subsets defined
by these two chromosomal abnormalities, we investigated the usage of V(H)
genes and the pattern of somatic mutation in 10 cases of trisomy 12 with
atypical morphology and eight cases of 13q14 abnormality with typical
morphology. In addition, four cases with both chromosomal abnormalities
were analyzed. Results confirm a common usage of the V(H)1 family in all
subsets. However, the patterns of somatic mutation were distinct, with
cases of trisomy 12 showing a minimal level of mutation (mean +/- SD, 0.34%
+/- 0.86%) and cases of 13q14 abnormality showing significant levels (6.5%
+/- 1.67%). The four cases with both abnormalities showed a mixed pattern.
All mutated cases had intraclonal homogeneity, and three of 10 had a
pattern indicative of antigen selection. These results suggest that the
clonal history of the two subsets of CLL may differ.
Volume 89,
Issue 11,
pp. 4153-4160,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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