Analysis of VH genes in marginal zone lymphoma reveals marked heterogeneity between splenic and nodal tumors and suggests the existence of clonal selection

Equipe Accueil 3737 Pathologie des Cellules Lymphoides, Universite Claude Bernard, France. BACKGROUND AND OBJECTIVES: To clarify the relationship between splenic (SMZL) and nodal marginal zone (NMZL) lymphomas, we analyzed immunoglobulin variable heavy chain (VH) gene usage and mutation patterns in...

Full description

Saved in:
Bibliographic Details
Published in:Haematologica (Roma) 2005-04, Vol.90 (4), p.470-478
Main Authors: Traverse-Glehen, A, Davi, F, Ben Simon, E, Callet-Bauchu, E, Felman, P, Baseggio, L, Gazzo, S, Thieblemont, C, Charlot, C, Coiffier, B, Berger, F, Salles, G
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Clonal Anergy - genetics
Female
Genes, Immunoglobulin - physiology
Hematologic and hematopoietic diseases
Humans
Immunoglobulin Heavy Chains - genetics
Immunoglobulin Variable Region - genetics
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphatic Diseases - blood
Lymphatic Diseases - genetics
Lymphoma, B-Cell - blood
Lymphoma, B-Cell - genetics
Male
Medical sciences
Middle Aged
Splenic Neoplasms - blood
Splenic Neoplasms - genetics
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Equipe Accueil 3737 Pathologie des Cellules Lymphoides, Universite Claude Bernard, France. BACKGROUND AND OBJECTIVES: To clarify the relationship between splenic (SMZL) and nodal marginal zone (NMZL) lymphomas, we analyzed immunoglobulin variable heavy chain (VH) gene usage and mutation patterns in these tumors. DESIGN AND METHODS: VH genes were cloned and sequenced from 49 lymphoma samples (35 SMZL and 14 NMZL). RESULTS: A biased usage of VH gene was found with overrepresentation of VH1 in SMZL cases (13/35) and VH4 in NMZL cases (7/14). Evidence for antigen driven mutations was identified in 8 SMZL and 4 NMZL cases. Three cases out of 18 with clones analyzed from spleen and peripheral blood demonstrated intra-clonal diversity, with evidence of clonal selection in one case, indicating the possibility of antigen-driven clonal expansion. Eleven SMZL cases (31%) but only 2 NMZL (14%) cases were unmutated. No differences in clinical outcome and overall survival were found between the unmutated and mutated cases. INTERPRETATION AND CONCLUSIONS: The pattern of somatic mutation and the VH gene segment usage appear to differ between SMZL and NMZL, suggesting that these are distinct pathological entities. Moreover, a biased usage of certain sequences suggests that tumor cells in SMZL may be subjected to antigen selection.
ISSN:0390-6078
1592-8721