A STUDY OF HTLV-1-RELATED DISEASES BY MEANS OF HIGHLY SENSITIVE HISTOCHEMISTRY

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This study aimed to see pathogenesis of HTLV-1-related diseases, especially adult T-cell leukemia/lymphoma (ATLL) by means of highly-sensitive histochemistry. Integrated HTLV-1 proviral DNA is the first target to be detected by means of the highly-sensitive histochemistry. But, because of degradation of DNA strands in paraffon sections of routinely processed tissue, the proviral DNA is not a good target to be detected in the sections. We established highly sensitive immunohistochemistry of HTLV-1 p40Tax (Tax), p27Rex (REx), and transcription factors in G1/S transition of cell cycle. By means of the highly-sensitive immunohistochemistry, the relation of expression of Tax and Rex and to the phenotypic transformation in ATLL cells, and to the expression of the transcription factors in G1/S transition of cell cycle. ATLL cells expressed much more Rex than Tax. ATLL cells did not expressed Tax in all phases of cell growth and proliferation. Highly-sensitive histochemical detection of Tax and Rex is useful in the differential diagnosis of ATLL from the other T-cell lymphomas. ATLL cells showed overexpression of one of E2F families in nucleus or no expression of them, whereas European cases of T-cell lymphomas without HTLV-1 infection showed overexpression of cyclin E. Expressing a small amount of Tax, ATLL cells expressed weakly cyclin E in asmall number of nuclei. Consequently, it was suggested that HTLV-1 leukemogenesis of ATLL focuses on the proliferation signal transduction system that ends to release E2F from retinoblastoma protein to nucleus in G1/S transition. On the other hand, ATLL cells suggested over-riding checkpoint abnormality in cell cycle, expressing a large amount of E2F in nuclei even in S phase of cell cycle in some cases. Tax expressed weakly expressed in ATLL cells was thought to induce weak expression of cyclin E in nucleus, although this expression of cyclin E is thought to be a part of preserved cell function.