Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies

R. C. Tschumper, Angela Dispenzieri, R. S. Abraham, K. J. Henderson, Diane F Jelinek

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LCmatched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis.

Original languageEnglish (US)
Article numbere112
JournalBlood Cancer Journal
Volume3
Issue number4
DOIs
StatePublished - Apr 2013

Fingerprint

Immunoglobulin Genes
Paraproteinemias
Light
Immunoglobulin Heavy Chains
Proteins
Complementarity Determining Regions
Polymerase Chain Reaction
Hematologic Diseases
Fluorescent Antibody Technique
Immunoglobulin M
Immunoglobulins
Mutation
Genes

Keywords

  • Biclonal
  • Clonality
  • IGHV
  • Monoclonal gammopathy

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies. / Tschumper, R. C.; Dispenzieri, Angela; Abraham, R. S.; Henderson, K. J.; Jelinek, Diane F.

In: Blood Cancer Journal, Vol. 3, No. 4, e112, 04.2013.

Research output: Contribution to journalArticle

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