MIAMI BEACHBy conventional karyotyping, the frequency of c-myc
dysregulation in multiple myeloma is low. Now, using molecular
karyotyping techniques, researchers have found c-myc chromosomal
abnormalities in multiple myeloma cell lines.
We have screened genomic DNA from 20 multiple myeloma cell
lines in our lab for mutations in c-myc exons, and in six of these,
we have found two genetically distinct c-myc allelesa normal
wildtype allele plus a polymorphic allele containing a silent
mutation, said Yaping Shou, MD, PhD, of the National Cancer
Institute, Medicine Branch. Although c-myc is overexpressed in
all six of these cell lines, only one c-myc allele is expressed,
Dr. Shou told Oncology News International at a poster session
of the 40th annual meeting of the American Society of Hematology
The researchers have also analyzed the corresponding primary tumor
cells in one of the six mutated cell lines and found only one c-myc
allele to be selectively expressed. By contrast, in three B
lymphoblastoid cell lines, both c-myc alleles are expressed to a
By conventional karyotyping, the researchers could find no structural
alteration of c-myc locus in the six multiple myeloma cell lines with
a mutation. Dr. Shou and her colleagues at the NCI, National Center
for Genome Research, and Cornell University Medical College then
began screening these cell lines for chromosomal abnormalities using
more sensitive fluorescent in situ hybridization (FISH) (see Figure)
and spectral karyotyping (SKY) analysis.
In the three cell lines examined to date by these techniques,
translocations involving the c-myc locus at 8q24 have been
identified. The partner chromosomes of these translocations include
chromosome 14 in the JJN3 cell line, chromosome 1 in OPM2, and an
unknown chromosome in MM1-144. It makes sense that the
translocated c-myc allele is the allele that is expressed in most
multiple myeloma cell lines, Dr. Shou said.
When Do Translocations Occur?
Dr. Shou said that the researchers need to finish screening their
cell lines for c-myc translocations and also determine the frequency
of c-myc translocations in myeloma patients and when during myeloma
development the translocations occur.
She pointed out that most of the cell lines her group is studying are
from the final leukemic stage of multiple myeloma, so we think
c-myc probably is important, not for tumor formation, but for tumor
development to the leukemic stage.
If it turns out to be true that c-myc translocation occurs only in
the final stage of the disease, she said, then researchers could
attempt to develop a therapeutic approach, possibly by antisense
technology, to block c-myc overepression, which in theory could stop
or slow tumor development to the final stage.