Immunoglobulin heavy chain sequence analysis in Waldenstrom's macroglobulinemia and immunoglobulin M monoclonal gammopathy of undetermined significance.
In this study, we used IGH sequence analysis to assess the maturational status of Waldenstrom's (WM) macroglobulinemia and its putative precursor immunoglobulin (Ig)-M monoclonal gammopathy of undetermined significance (MGUS). IGH sequence analysis was performed using standard methods in 23 cases (20 WM and 3 IgM MGUS as defined by consensus panel criteria). Waldenstrom's macroglobulinemia cases were characterized by heavily mutated IGH genes (median, 6.3%; range, 3.8%-13.9%) but without intraclonal variation (ICV). IgM MGUS was similarly characterized by somatic hypermutation (median, 7.5%; range, 7%-7.7%), but ICV was evident in 1 of the 3 cases. We would therefore conclude that WM is characterized by somatic hypermutation without ICV, which supports a derivation from postgerminal center/memory B cells. IgM MGUS is also characterized by somatic hypermutation but, in a manner similar to IgA/IgG MGUS, can be associated with ICV, although the significance of this remains unclear.
Rollett
Rebecca A
RA
HMDS Laboratory, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Wilkinson
Elizabeth J
EJ
Gonzalez
David
D
Fenton
James A L
JA
Short
Michael A
MA
Evans
Paul A S
PA
Rawstron
Andy C
AC
Owen
Roger G
RG
D000368:Aged; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000235:genetics; D007075:Immunoglobulin M / Q000737:chemistry* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010265:Paraproteinemias / Q000235:genetics / Q000276:immunology*; D017422:Sequence Analysis, DNA; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M