Immunoglobulin V(H) gene mutational analysis suggests that blastic variant of mantle cell lymphoma derives from different stages of B-cell maturation

Terézia László, Mónika Nagy, Gábor Kelényi, A. Matolcsy

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

To characterise the nature of the cellular origin of the blastic variant of mantle cell lymphoma (MCL-BV), we analysed the immunoglobulin (Ig) heavy chain variable region (V(H)) genes in four cases of MCL-BV. The rearranged V(H)-D-J(H) genes were PCR-amplified, cloned and sequenced. In one case, the comparison of the rearranged V(H) gene sequence to known germline V(H) gene templates showed no somatic mutations suggesting a pre-germinal centre B-cell origin for tumour cells. In the other three cases, the V(H) gene sequences showed varied number of point mutations relative to the putative germline V(H) gene sequences but the point mutations were not associated with intraclonal diversification. In one of the mutated cases, the distribution and type of the mutations indicated that tumour cells had been selected by an antigen. Since somatically mutated Ig genes are expressed by B-cells that have reached a germinal centre/post-germinal centre stage of development, these findings suggest that the MCL-BV cell of origin may also be a germinal centre or a post-germinal centre B-cell. Taken together, our findings suggest that the development of MCL-BC may not be restricted to one stage of B-cell differentiation and that they may represent transformants of B-cells at different stages of ontogeny.

Original languageEnglish
Pages (from-to)27-31
Number of pages5
JournalLeukemia Research
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 2000

Fingerprint

Immunoglobulin Variable Region
Mantle-Cell Lymphoma
Germinal Center
B-Lymphocytes
Genes
Point Mutation
Immunoglobulin Heavy Chains
Immunoglobulin Genes
Mutation
Cell Differentiation
Neoplasms
Antigens
Polymerase Chain Reaction

Keywords

  • Immunoglobulin gene
  • Mantle cell lymphoma blastic variant
  • Somatic mutation

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Immunoglobulin V(H) gene mutational analysis suggests that blastic variant of mantle cell lymphoma derives from different stages of B-cell maturation. / László, Terézia; Nagy, Mónika; Kelényi, Gábor; Matolcsy, A.

In: Leukemia Research, Vol. 24, No. 1, 01.2000, p. 27-31.

Research output: Contribution to journalArticle

@article{50ddb10c92314718b1f69bae0e722bf7,
title = "Immunoglobulin V(H) gene mutational analysis suggests that blastic variant of mantle cell lymphoma derives from different stages of B-cell maturation",
abstract = "To characterise the nature of the cellular origin of the blastic variant of mantle cell lymphoma (MCL-BV), we analysed the immunoglobulin (Ig) heavy chain variable region (V(H)) genes in four cases of MCL-BV. The rearranged V(H)-D-J(H) genes were PCR-amplified, cloned and sequenced. In one case, the comparison of the rearranged V(H) gene sequence to known germline V(H) gene templates showed no somatic mutations suggesting a pre-germinal centre B-cell origin for tumour cells. In the other three cases, the V(H) gene sequences showed varied number of point mutations relative to the putative germline V(H) gene sequences but the point mutations were not associated with intraclonal diversification. In one of the mutated cases, the distribution and type of the mutations indicated that tumour cells had been selected by an antigen. Since somatically mutated Ig genes are expressed by B-cells that have reached a germinal centre/post-germinal centre stage of development, these findings suggest that the MCL-BV cell of origin may also be a germinal centre or a post-germinal centre B-cell. Taken together, our findings suggest that the development of MCL-BC may not be restricted to one stage of B-cell differentiation and that they may represent transformants of B-cells at different stages of ontogeny.",
keywords = "Immunoglobulin gene, Mantle cell lymphoma blastic variant, Somatic mutation",
author = "Ter{\'e}zia L{\'a}szl{\'o} and M{\'o}nika Nagy and G{\'a}bor Kel{\'e}nyi and A. Matolcsy",
year = "2000",
month = "1",
doi = "10.1016/S0145-2126(99)00156-3",
language = "English",
volume = "24",
pages = "27--31",
journal = "Leukemia Research",
issn = "0145-2126",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - Immunoglobulin V(H) gene mutational analysis suggests that blastic variant of mantle cell lymphoma derives from different stages of B-cell maturation

AU - László, Terézia

AU - Nagy, Mónika

AU - Kelényi, Gábor

AU - Matolcsy, A.

PY - 2000/1

Y1 - 2000/1

N2 - To characterise the nature of the cellular origin of the blastic variant of mantle cell lymphoma (MCL-BV), we analysed the immunoglobulin (Ig) heavy chain variable region (V(H)) genes in four cases of MCL-BV. The rearranged V(H)-D-J(H) genes were PCR-amplified, cloned and sequenced. In one case, the comparison of the rearranged V(H) gene sequence to known germline V(H) gene templates showed no somatic mutations suggesting a pre-germinal centre B-cell origin for tumour cells. In the other three cases, the V(H) gene sequences showed varied number of point mutations relative to the putative germline V(H) gene sequences but the point mutations were not associated with intraclonal diversification. In one of the mutated cases, the distribution and type of the mutations indicated that tumour cells had been selected by an antigen. Since somatically mutated Ig genes are expressed by B-cells that have reached a germinal centre/post-germinal centre stage of development, these findings suggest that the MCL-BV cell of origin may also be a germinal centre or a post-germinal centre B-cell. Taken together, our findings suggest that the development of MCL-BC may not be restricted to one stage of B-cell differentiation and that they may represent transformants of B-cells at different stages of ontogeny.

AB - To characterise the nature of the cellular origin of the blastic variant of mantle cell lymphoma (MCL-BV), we analysed the immunoglobulin (Ig) heavy chain variable region (V(H)) genes in four cases of MCL-BV. The rearranged V(H)-D-J(H) genes were PCR-amplified, cloned and sequenced. In one case, the comparison of the rearranged V(H) gene sequence to known germline V(H) gene templates showed no somatic mutations suggesting a pre-germinal centre B-cell origin for tumour cells. In the other three cases, the V(H) gene sequences showed varied number of point mutations relative to the putative germline V(H) gene sequences but the point mutations were not associated with intraclonal diversification. In one of the mutated cases, the distribution and type of the mutations indicated that tumour cells had been selected by an antigen. Since somatically mutated Ig genes are expressed by B-cells that have reached a germinal centre/post-germinal centre stage of development, these findings suggest that the MCL-BV cell of origin may also be a germinal centre or a post-germinal centre B-cell. Taken together, our findings suggest that the development of MCL-BC may not be restricted to one stage of B-cell differentiation and that they may represent transformants of B-cells at different stages of ontogeny.

KW - Immunoglobulin gene

KW - Mantle cell lymphoma blastic variant

KW - Somatic mutation

UR - http://www.scopus.com/inward/record.url?scp=0344614634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344614634&partnerID=8YFLogxK

U2 - 10.1016/S0145-2126(99)00156-3

DO - 10.1016/S0145-2126(99)00156-3

M3 - Article

VL - 24

SP - 27

EP - 31

JO - Leukemia Research

JF - Leukemia Research

SN - 0145-2126

IS - 1

ER -