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Differential rates of somatic hypermutation in V(H) genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities

Differential rates of somatic hypermutation in V(H) genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities
Differential rates of somatic hypermutation in V(H) genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities
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 VH 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 VH1 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
0006-4971
4153-4160
Oscier, D.G.
c2620a1d-25bb-48f7-9651-f5d023636381
Thompsett, A.
9b2c11bc-4a83-462b-a27e-978f97152189
Zhu, D.
4f4f12ef-d220-4a7b-a1a0-63c6b66b9e17
Stevenson, F.K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Oscier, D.G.
c2620a1d-25bb-48f7-9651-f5d023636381
Thompsett, A.
9b2c11bc-4a83-462b-a27e-978f97152189
Zhu, D.
4f4f12ef-d220-4a7b-a1a0-63c6b66b9e17
Stevenson, F.K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

Oscier, D.G., Thompsett, A., Zhu, D. and Stevenson, F.K. (1997) Differential rates of somatic hypermutation in V(H) genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities. Blood, 89 (11), 4153-4160. (PMID:9166858)

Record type: Article

Abstract

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 VH 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 VH1 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

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Published date: 1 June 1997
Organisations: Cancer Sciences

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Local EPrints ID: 361912
URI: http://eprints.soton.ac.uk/id/eprint/361912
ISSN: 0006-4971
PURE UUID: 576e0f06-bb5c-4530-b2c7-625a696d08ef
ORCID for F.K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 07 Feb 2014 09:25
Last modified: 23 Jul 2022 01:41

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Contributors

Author: D.G. Oscier
Author: A. Thompsett
Author: D. Zhu
Author: F.K. Stevenson ORCID iD

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