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Blood, 15 August 2002, Vol. 100, No. 4, pp. 1505-1507
BRIEF REPORT
Typical Waldenstrom macroglobulinemia is derived from a B-cell
arrested after cessation of somatic mutation but prior to isotype
switch events
Surinder S. Sahota,
Francesco Forconi,
Christian H. Ottensmeier,
Drew Provan,
David G. Oscier,
Terry J. Hamblin, and
Freda K. Stevenson
From the Molecular Immunology Group, Tenovus
Laboratory, Southampton University Hospitals, Southampton, United
Kingdom; Department of Haematology, St Bartholomew's and The Royal
London School of Medicine and Dentistry, London, United Kingdom;
Department of Haematology, Royal Bournemouth Hospital, Bournemouth,
United Kingdom.
There exists a wide spectrum of IgM-secreting B-cell tumors with
different clinical behavior. Knowledge of the VH 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. VH 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.
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