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The expression of platelet-derived growth factor (PDGF) is controlled in a very complicated manner. To clarify the mechanism of regulation of the PDGF-A chain gene, deletion analysis of the 5'-flanking region was performed. We identified a positive regulatory element 25 base pairs (bp) upstream of TATAA, a negative element 135 bp upstream, a positive element 223 bp upstream and a negative element further upstream. These regulatory sites of the PDGF-A chain gene may be involved in tissue specificity, developmental regulation, and transformation. In addition, our analysis suggested the presence of a strand non-specific single-stranded DNA binding nuclear protein in the positive regulatory element 25 bp upstream of TATAA.

Follicular lymphoma is a low grade malignant lymphoma. However, some follicular lymphomas undergo histological transformation into higher grade malignant lymphomas. We recently encountered a diffuse large cell lymphoma which seemed to have progressed from a follicular lymphoma and which finally transformed into a small non-cleaved lymphoma. Each stage of the histological transformation was accompanied by increasing clinical grades of malignancy. It was suspected that in our patient a follicular lymphoma initially developed due to rearrangement of the BCL2 gene, and then underwent histological transformation into a diffuse large cell lymphoma, which was associated with p53 mutation. Subsequent rearrangement of C-MYC promoted the histological transformation of this diffuse large cell lymphoma into a small non-cleaved lymphoma. Our findings indicate that p53 mutation and rearrangement of C-MYC are involved in the histological transformation of follicular lymphomas into more advanced lymphomas.

The relationship between immunophenotype, histopathology and clinical stage in influencing prognosis was evaluated in 99 cases of non-Hodgkin's lymphoma (NHL). All cases were histopathologically classified according to the system of the international conference on working formulation (WF), immunologically analysed by flow cytometry with a panel of monoclonal antibodies and clinically staged by the Ann Arbor scheme. Eighty eight percent of T- and 87.7% of B-phenotype NHLs respectively received combination chemotherapies with or without radiotherapy. Early stages I and II showed higher response rates (86% for T- and B-NHL) compared to the advanced ones III and IV (58% for T-NHL and 65% for the B-NHLs), p<0.05. Higher overall survival rates were observed in low and intermediate grade NHLs, p < 0.05. The early stages further showed relatively higher survival rates in T- than in B-phenotype of intermediate grade NHL. Low grade NHL had the highest survival rates in both early and advanced stages, whereas the survival rate was the lowest in high grade NHL irrespective of the clinical stages. Immunophenotype, pathological grade and clinical stage jointly displayed varied predictive values in the prognosis of NHL. Since the present prognostic models are based on histological and staging criteria only, the results suggest that, phenotype should be included in the classification systems or prognostic models for the NHLs, thus facilitating the establishment of effective lineage specific therapies.

Human platelet-derived growth factor (PDGF) B chain is a cellular homologue of v-sis, closely involved in cell growth and oncogenicity. Analysis in this study showed the importance of not only the region near the TATAA box but also the fragment －355 bases or more upstream in the expression of the PDGF-B chain gene. However, tissue specificity was not clear in the 5' upstream region alone, and regulation by gene methylation or by elements other than in the 5' region seemed to be necessary. In A172 cells, the half-life of mRNA was much shorter in the PDGF-B chain (<2 hours) than in the PDGF-A chain (7 hours). Regulation of the PDGF-B chain gene may markedly differ from that of the PDGF-A chain gene not only at the transcriptional level but also at the post-transcriptional level.

We have isolated and characterized genomic clones of the 5' region of the human PDGF A-chain gene. The putative "TATAA" box was identified 876 bp upstream of the translation initiation site. A significant number of potential regulatory elements were identified in DNA sequences upstream of the "TATAA" box and were also found within the intrans sequenced. The DNA sequence results differ significantly from those reported for the PDGF B-chain gene, suggesting a basis for the expression of the PDGF A-chain gene and the B-chain gene under very different conditions.

Platelet-derived growth factor (PDGF) is a heterodimeric glycoprotein consisting of A and B chains. A functional promoter had been identified in the 5' flanking region of the human PDGF-A chain gene. We found that the PDGF-A chain promoter region possesses the potential for bidirectional activity. This bidirectional promoter activity is influenced by the 5' -untranslated region (5'-UTR) and serum concentration. The 5'-UTR may regulate expression of the PDGF-A chain by transcription in the opposite direction.