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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A021
Somatic recombination of immunoglobulin V genes creates unique sequences
in the joining regions, which are clonal markers for B cells. Thus, PCR
amplification and subsequent direct sequencing of rearranged V gene segments
allows the analysis of clonal relationships between single cells. As
rearranged immunoglobulins of B cells participating in a germinal center
reaction are somatically mutated, such analysis allows also the assignment
of the lymphoma precursor cells to a pre- or post-germinal center stage or,
if ongoing mutation is detected, to mutating germinal center B cells. Using
this approch we have recently analysed six cases of T cell-rich B cell
lymphoma. In all cases a mutating germinal center B cell, which seems to be
selected for expression of a functional antigen receptor, was identified as
the lymphoma precursor. In addition, we analysed the clonal relationship of
the Hodgkin/Reed-Sternberg cells of Hodgkins disease (HD) and the neoplastic
cells of non Hodgkin lymphomas (NHL) occuring in the same patient. In one
case HD and Follicular lymphoma were found simultaneous in one lymphe node,
whereas in another case T cell-rich B cell lymphoma of the skin (surgical
removed without further therapy) was followed by HD three years later.
Analysis of the rearranged V genes from the CD20 positive cells of the NHLs
and CD30 positive cells of the HDs revealed clonal relationships between
the NHLs and HDs in both cases. The rearranged V genes in the two different
lymphomas of each case carried shared as well as unique mutations.
Intraclonal diversity due to ongoing mutation was observed in both NHLs
but was absent or only marginal in both HDs. These findings provide further
evidence for the B cell origin of Hodgkin/Reed-Sternberg cells and indicate
that, at least in the two cases analysed, NHLs and HDs may share some common
transforming events.
IMMUNOGLOBULIN V GENE REARRANGEMENTS AS CLONAL MARKERS FOR MICROMANIPULATED
SINGLE CELLS FROM MALIGNANT LYMPHOMAS
Bräuninger A, Hansmann ML
Dept.Pathology,University of Frankfurt, Germany