Expression of the c-myc proto-oncogene in multiple myeloma and chronic
lymphocytic leukemia: an in situ analysis
R Greil, B Fasching, P Loidl and H Huber
Department of Internal Medicine, University of Innsbruck, Austria.
The c-myc gene plays a pivotal role in mediating the competence state for
cell cycle transversion. This biologic role is in contradiction to reports
of elevated expression of the gene in multiple myeloma, a tumor with
restricted self-renewal capacity. To more clearly define the role of this
gene in plasma cells of myeloma patients, c-myc messenger RNA (mRNA) and/or
oncoprotein expression were semiquantitatively analyzed on the single cell
level in 19 cases of multiple myeloma, among them 1 biclonal case and 1
case with coexistent chronic lymphocytic leukemia (CLL). Performing
anti-sense/mRNA in situ hybridization, mature c-myc gene transcripts were
detected in 92% (12 of 13) of cases and could definitely be attributed to
the plasma cells by our study. The number of Ki 67-positive plasma cells
actively passing the cell cycle was less than 1% and independent of c-myc
gene expression. However, because the presence of the 152-c-MYC epitope was
correlated to extent of marrow plasmacytosis (r = .64; P = .043) and
content of plasmablasts (P = .09), the c-myc gene might serve a function
different from proliferative activity, but also associated with tumor cell
mass. In CLL cells (21 of 22 cases) and their benign counterparts, ie, bone
marrow and peripheral blood lymphocytes, the anti-sense/c-myc mRNA
hybridization signals remained below the threshold considered as cutpoint
between negative and positive. The low amounts of c-myc transcripts were
correlated to neither stage of disease (P = .52) nor lymphocyte counts (P =
.24). Because the numbers of peripheral blood lymphoma cells were
independent of tumor mass and of c-myc gene transcripts expressed,
peripheral blood lymphocytosis might more likely reflect homing processes
than proliferative activity in CLL.
Volume 78,
Issue 1,
pp. 180-191,
07/01/1991
Copyright © 1991 by The American Society of Hematology
