title: IgG-secreting lymphoplasmacytoid leukaemia: a B-cell disorder with extensively mutated VH genes undergoing Ig isotype-switching frequently associated with trisomy 12.
abstract: We investigated 16 patients with elevated serum monoclonal IgG and a leukaemic B-cell lymphocytic disorder different from multiple myeloma. Their clinical history was that of a non-aggressive disease with dominant splenomegaly and long survival. Whereas abnormal blood and bone marrow cells were predominantly small lymphocytes with a few lymphoplasmacytoid cells, histopathological features included a lymphoplasmacytic infiltrate in eight cases. Most frequently, abnormal blood cells displayed a CD19+CD5-CD23+/- immunophenotype different from that of chronic lymphocytic leukaemia, except in two cases with a CD19+CD5+CD23+ phenotype. Interestingly, a coexistent serum monoclonal IgM and/or surface IgMG+ with identical light chain was identified in 10 patients, whereas in the remaining six patients only IgG expression was determined. VH gene analysis was performed in eight patients to investigate the clonal origins of tumour cells. All cases utilized the VH3 family, with evidence of extensive somatic mutations and intraclonal homogeneity in all cases. VH gene analysis indicated a clonal relationship between cells expressing IgM and IgG, with one case being biclonal. Cytogenetic evaluation showed a high incidence of trisomy 12 (60%) and 13q14 deletion (40%). In conclusion, we have described an unusual subset of low-grade lymphoma with high-serum IgG and frequent lymphoplasmacytoid features in which tumour cells derive from post-follicular memory B cells undergoing isotype switching with some cases arrested at both the IgM and IgG stage and others as IgG-positive cells only.
authors.affiliation: Laboratoire d'Hématologie, Institut de Biologie, Centre Hospitalier Universitaire, Nantes, France. richard.garand@chu-nantes.fr
authors.forename: R
authors.initials: R
authors.lastname: Garand
authors.forename: S S
authors.initials: SS
authors.lastname: Sahota
authors.forename: H
authors.initials: H
authors.lastname: Avet-Loiseau
authors.forename: P
authors.initials: P
authors.lastname: Talmant
authors.forename: N
authors.initials: N
authors.lastname: Robillard
authors.forename: A
authors.initials: A
authors.lastname: Moreau
authors.forename: F
authors.initials: F
authors.lastname: Gaillard
authors.forename: F K
authors.initials: FK
authors.lastname: Stevenson
authors.forename: R
authors.initials: R
authors.lastname: Bataille
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D020732:Cytogenetic Analysis; D005260:Female; D017353:Gene Deletion; D005803:Genes, Immunoglobulin; D006801:Humans; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology*; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology*; D007952:Leukemia, Plasma Cell / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D014314:Trisomy
chemical_list: D007074:Immunoglobulin G