The Ig Heavy Chain 3
End Confers a Posttranscriptional
Processing Advantage to Bcl-2-IgH Fusion RNA in t(14;18) Lymphoma
Alexander Scheidel Petrovic,
Robert L.Young, Bernadette Hilgarth,
Peter Ambros,
Stanley J. Korsmeyer, and
Ulrich Jaeger
From the Department of Medicine I, Division of Hematology, University
of Vienna Medical School, Vienna, Austria; the Howard Hughes Medical
Institute, Washington University School of Medicine, St Louis, MO; and
CCRI, St Anna Children's Hospital, Vienna, Austria.
The chromosomal translocation t(14;18) in lymphoma leads to an
overproduction of the Bcl-2 protein on the basis of increased Bcl-2
mRNA levels. Whereas the juxtaposition of Bcl-2 with the Ig heavy chain
locus causes a transcriptional activation, 70% of the lymphomas also
produce Bcl-2-Ig fusion RNAs with Ig 3
ends. Using S1 nuclease
protection assays that can discriminate between nuclear RNA precursors
and spliced mRNA, we found that the fusion RNAs in t(14;18) cell lines
exhibit an additional posttranscriptional processing advantage.
Transfection experiments with artificial genes containing various Bcl-2
or Ig 3 ends show that this effect is (1) related to RNA
splicing and/or nucleocytoplasmic transport; (2) independent of
transcriptional activation by the heavy chain enhancer; (3) dependent
on the presence of the JH-CH and C-
1 Ig
introns; and (4) tissue specific for B cells. This constitutes a novel
mechanism of oncogene deregulation unrelated to transcriptional activation or half-life prolongation. The data further support the
existence of a tissue-specific posttranscriptional pathway of Ig
regulation in B cells.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3952-3961
© 1998 by The American Society of Hematology.
