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Unmutated immunoglobulin VH genes are associated with a more aggressive form of chronic lymphocyte leukemia

Unmutated immunoglobulin VH genes are associated with a more aggressive form of chronic lymphocyte leukemia
Unmutated immunoglobulin VH genes are associated with a more aggressive form of chronic lymphocyte leukemia
Despite having several characteristics of na??ve B cells, chronic lymphocytic leukemia (CLL) cells have been shown in some cases to have somatically mutated Ig variable region genes, indicating that the cell of origin has passed through the germinal center. A previous study of patients with CLL found an association between lack of somatic mutation and trisomy 12 and, therefore, possibly with a less favorable prognosis. We have sequenced the Ig VH genes of the tumor cells of 84 patients with CLL and correlated our findings with clinical features. A total of 38 cases (45.2%) showed ? 98% sequence homology with the nearest germline VH gene; 46 cases (54.8%) showed >2% somatic mutation. Unmutated VH genes were significantly associated with V1-69 and D3-3 usage, with atypical morphology; isolated trisomy 12, advanced stage and progressive disease. Survival was significantly worse for patients with unmutated VH genes irrespective of stage. Median survival for stage A patients with unmutated VH genes was 95 months compared with 293 months for patients whose tumors had mutated VHgenes (P = .0008). The simplest explanation is that CLL comprises 2 different diseases with different clinical courses. One, arising from a memory B cell, has a benign course, the other, arising from a na??ve B cell, is more malignant
0006-4971
1848-1854
Hamblin, T.J.
85c9639a-7cf1-4477-9267-e6d772ba66ab
Davis, Z.
b106965c-11bb-4133-98f0-540894dd11a9
Gardiner, A.
0c87983a-019a-4206-842b-ad12603b99e4
Oscier, D.G.
c2620a1d-25bb-48f7-9651-f5d023636381
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Hamblin, T.J.
85c9639a-7cf1-4477-9267-e6d772ba66ab
Davis, Z.
b106965c-11bb-4133-98f0-540894dd11a9
Gardiner, A.
0c87983a-019a-4206-842b-ad12603b99e4
Oscier, D.G.
c2620a1d-25bb-48f7-9651-f5d023636381
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

Hamblin, T.J., Davis, Z., Gardiner, A., Oscier, D.G. and Stevenson, Freda K. (1999) Unmutated immunoglobulin VH genes are associated with a more aggressive form of chronic lymphocyte leukemia. Blood, 94 (6), 1848-1854. (PMID:10477713)

Record type: Article

Abstract

Despite having several characteristics of na??ve B cells, chronic lymphocytic leukemia (CLL) cells have been shown in some cases to have somatically mutated Ig variable region genes, indicating that the cell of origin has passed through the germinal center. A previous study of patients with CLL found an association between lack of somatic mutation and trisomy 12 and, therefore, possibly with a less favorable prognosis. We have sequenced the Ig VH genes of the tumor cells of 84 patients with CLL and correlated our findings with clinical features. A total of 38 cases (45.2%) showed ? 98% sequence homology with the nearest germline VH gene; 46 cases (54.8%) showed >2% somatic mutation. Unmutated VH genes were significantly associated with V1-69 and D3-3 usage, with atypical morphology; isolated trisomy 12, advanced stage and progressive disease. Survival was significantly worse for patients with unmutated VH genes irrespective of stage. Median survival for stage A patients with unmutated VH genes was 95 months compared with 293 months for patients whose tumors had mutated VHgenes (P = .0008). The simplest explanation is that CLL comprises 2 different diseases with different clinical courses. One, arising from a memory B cell, has a benign course, the other, arising from a na??ve B cell, is more malignant

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Published date: 15 September 1999
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 361909
URI: http://eprints.soton.ac.uk/id/eprint/361909
ISSN: 0006-4971
PURE UUID: 1b7db85f-fd50-4ca9-826a-c25a827efcc2
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 07 Feb 2014 09:16
Last modified: 17 Dec 2019 01:57

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Contributors

Author: T.J. Hamblin
Author: Z. Davis
Author: A. Gardiner
Author: D.G. Oscier

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