title: Typical Waldenstrom macroglobulinemia is derived from a B-cell arrested after cessation of somatic mutation but prior to isotype switch events.
abstract: There exists a wide spectrum of IgM-secreting B-cell tumors with different clinical behavior. Knowledge of the V(H) gene status can reveal their origin and clonal history. For Waldenstrom macroglobulinemia (WM), a distinct subtype of lymphoplasmacytic lymphoma, early data on limited sequences showed evidence for somatic mutation. A recent report of one case demonstrated intraclonal mutational activity occurring after transformation, a characteristic of germinal center lymphomas. To extend the investigation, we have analyzed 7 cases of WM. V(H) genes were somatically mutated with no evidence of intraclonal variation in all cases. In contrast to IgM-secreting multiple myeloma, there was no evidence for isotype switch transcripts in any of the cases. These data support the concept that typical WM is derived from a B cell that has undergone somatic mutation prior to transformation, at a point where isotype switch events have not been initiated. (Blood. 2002;100:1505-1507)
authors.affiliation: Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, Southampton, United Kingdom. s.s.sahota@soton.ac.uk
authors.forename: Surinder S
authors.initials: SS
authors.lastname: Sahota
authors.forename: Francesco
authors.initials: F
authors.lastname: Forconi
authors.forename: Christian H
authors.initials: CH
authors.lastname: Ottensmeier
authors.forename: Drew
authors.initials: D
authors.lastname: Provan
authors.forename: David G
authors.initials: DG
authors.lastname: Oscier
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Hamblin
authors.forename: Freda K
authors.initials: FK
authors.lastname: Stevenson
mesh_terms: D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D007075:Immunoglobulin M / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics* / Q000276:immunology
chemical_list: D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region