Distinctive features of immunoglobulin heavy chain variable region gene rearrangement in multiple myeloma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97336
Title:
Distinctive features of immunoglobulin heavy chain variable region gene rearrangement in multiple myeloma.
Authors:
Baker, Bartrum W; Deane, M; Gilleece, Maria H; Johnston, Diane; Scarffe, J Howard; Norton, John D
Abstract:
We have analysed the rearranged Ig heavy chain (IgH) genes in a series of 28 cases of multiple myeloma (MM), in order to extend the study of Ig heavy chain variable (VH) gene usage in B lymphoid malignancies and to explore the ontogenic compartment from which transformed precursor cells arise in this disease. We were able to amplify 28 rearranged alleles by polymerase chain reaction from 23 of these cases, using a common joining region (JH) amplimer together with a panel of VH family-specific amplimers. The pattern of VH family usage was similar to that reported in normal peripheral blood B cells with infrequent usage of VH5 and VH6 genes. However, nucleotide sequence analysis of 17 IgH alleles revealed rearrangement of other VH family members, closely related to known developmentally regulated VH genes, some of which are known to be associated with autoimmune specificities. In contrast to previous findings on more immature B lineage malignancies, the rearranged genes diverged extensively from consensus germline sequences, consistent with somatic mutation. These findings support the hypothesis that the major proliferating precursor in MM arises at, or following a stage of T cell-dependent germinal centre proliferation in lymphoid follicles.
Affiliation:
CRC Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Distinctive features of immunoglobulin heavy chain variable region gene rearrangement in multiple myeloma. 1994, 14 (3-4):291-301 Leuk. Lymphoma
Journal:
Leukemia & Lymphoma
Issue Date:
Jul-1994
URI:
http://hdl.handle.net/10541/97336
DOI:
10.3109/10428199409049681
PubMed ID:
7950918
Type:
Article
Language:
en
ISSN:
1042-8194
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBaker, Bartrum Wen
dc.contributor.authorDeane, Men
dc.contributor.authorGilleece, Maria Hen
dc.contributor.authorJohnston, Dianeen
dc.contributor.authorScarffe, J Howarden
dc.contributor.authorNorton, John Den
dc.date.accessioned2010-04-26T08:57:48Z-
dc.date.available2010-04-26T08:57:48Z-
dc.date.issued1994-07-
dc.identifier.citationDistinctive features of immunoglobulin heavy chain variable region gene rearrangement in multiple myeloma. 1994, 14 (3-4):291-301 Leuk. Lymphomaen
dc.identifier.issn1042-8194-
dc.identifier.pmid7950918-
dc.identifier.doi10.3109/10428199409049681-
dc.identifier.urihttp://hdl.handle.net/10541/97336-
dc.description.abstractWe have analysed the rearranged Ig heavy chain (IgH) genes in a series of 28 cases of multiple myeloma (MM), in order to extend the study of Ig heavy chain variable (VH) gene usage in B lymphoid malignancies and to explore the ontogenic compartment from which transformed precursor cells arise in this disease. We were able to amplify 28 rearranged alleles by polymerase chain reaction from 23 of these cases, using a common joining region (JH) amplimer together with a panel of VH family-specific amplimers. The pattern of VH family usage was similar to that reported in normal peripheral blood B cells with infrequent usage of VH5 and VH6 genes. However, nucleotide sequence analysis of 17 IgH alleles revealed rearrangement of other VH family members, closely related to known developmentally regulated VH genes, some of which are known to be associated with autoimmune specificities. In contrast to previous findings on more immature B lineage malignancies, the rearranged genes diverged extensively from consensus germline sequences, consistent with somatic mutation. These findings support the hypothesis that the major proliferating precursor in MM arises at, or following a stage of T cell-dependent germinal centre proliferation in lymphoid follicles.en
dc.language.isoenen
dc.subject.meshBase Sequence-
dc.subject.meshGene Rearrangement-
dc.subject.meshHumans-
dc.subject.meshImmunoglobulin Heavy Chains-
dc.subject.meshImmunoglobulin Variable Region-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMultiple Myeloma-
dc.subject.meshPolymerase Chain Reaction-
dc.titleDistinctive features of immunoglobulin heavy chain variable region gene rearrangement in multiple myeloma.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalLeukemia & Lymphomaen

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