Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia

Despite having several characteristics of naïve 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...

Full description

Saved in:
Bibliographic Details
Published in:Blood 1999-09, Vol.94 (6), p.1848-1854
Main Authors: Hamblin, T J, Davis, Z, Gardiner, A, Oscier, D G, Stevenson, F K
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
B-Lymphocytes - immunology
Chromosomes, Human, Pair 12
Female
Follow-Up Studies
Genes, Immunoglobulin
Humans
Immunoglobulin Heavy Chains - genetics
Immunoglobulin Variable Region - genetics
Immunologic Memory
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - immunology
Leukemia, Lymphocytic, Chronic, B-Cell - mortality
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Male
Middle Aged
Mutation
Neoplasm Staging
Prognosis
Retrospective Studies
Survival Analysis
Time Factors
Trisomy
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Despite having several characteristics of naïve 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 V(H) 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 V(H) gene; 46 cases (54.8%) showed >2% somatic mutation. Unmutated V(H) 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 V(H) genes irrespective of stage. Median survival for stage A patients with unmutated V(H) genes was 95 months compared with 293 months for patients whose tumors had mutated V(H) genes (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 naïve B cell, is more malignant.
ISSN:0006-4971
DOI:10.1182/blood.v94.6.1848