Alterations of p53 and c-myc in the clonal evolution of malignant lymphoma
H Chang, S Benchimol, MD Minden and HA Messner
Ontario Cancer Institute, University of Toronto, Ontario, Canada.
We derived the lymphoma cell lines OCI-Ly 13.1 and OCI-Ly 13.2 from a
patient with non-Hodgkin's lymphoma at the time of presentation and during
chemotherapy-resistant relapse. These lines were of T-cell phenotype and
contained the identical T-cell receptor beta-chain rearrangement,
indicating that both lines were members of the same malignant clone. The
lines differed in their growth characteristics; OCI-Ly 13.1 grew slowly and
required growth factors for colony formation, whereas OCI-Ly 13.2 grew
rapidly and formed colonies without addition of growth factors. To test
whether or not these biologic differences were associated with specific
genetic changes, we evaluated the status of the c-myc and p53 genes of both
cell lines. The p53 and c- myc genes of OCI-Ly 13.1 were in germline
configuration and produced normal-sized transcripts. The p53 protein
expressed in OCI-Ly 13.1 was recognized by the anti-p53 monoclonal
antibody, PAb240, indicating a conformation typical of p53 proteins
expressed by p53 alleles containing a missense mutation. However,
sequencing studies of the entire p53 coding region did not reveal any point
mutations. In contrast, the cell line OCI-Ly 13.2 contained structural
abnormalities of both the c-myc and p53 genes. In addition, one of the p53
alleles was lost as determined by a cDNA probe for the p53 gene (17p 13.1)
and the YNZ22.1 probe (17p 13.3). These changes resulted in the absence of
p53 protein and mRNA in OCI-Ly 13.2 as detected by immunoprecipitation and
Northern blot analysis, respectively. They may be a reflection of disease
progression and may be associated with the altered behavior of the
malignant cell population within the patient and in vitro.
Volume 83,
Issue 2,
pp. 452-459,
01/15/1994
Copyright © 1994 by The American Society of Hematology
