ANALYSIS OF TRANSCRIPTIONAL REGUlATION IN ADULT T-CELL LEUKEMIA

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09671134
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: TEIKYO UNIVERSITY
• Principal Investigator: NISHIDA Junji TEIKYO UNIVERSITY SCHOOL OF MEDICINE, INTERNAL MEDICiNE, ASSOCIATE PROFESSOR, 医学部, 助教授 (80228189)
• Project Period (FY): 1997 – 1998
• Keywords: adult T-cell leukemia / transcription factor / transcriptional regulation

Research Abstract

I reported previously abnormal expression of two transcription factors, ISCAT and GATA-4, in adult T-cell leukemia cell lines. In this study, as the next step, I examined the relationship of these two factors and leukemogenesis in two approaches : (1) detection of mRNA expression factors in ATL cells.
(1) Total RNA from twenty-two clinical samples (two adult T-cell leukemia, four leukemic transformation of malignant lymphoma, six chronic myelogenous leukemia, nine multiple myeloma and one hairy cell leukemia) were purified and RT-PCR was performed. No amplification was observed in each samples. Because those factors were identified to bind the promoter of interleukin 5 in ATL cells, the message might not be detected in cells which do not significance of these factors in leukemogenesis. Viral infection is another possible candidate in which those transcription factors may be relevant to pathogenesis, because ISCAT was expressed in EBV-infected cell lines as well as ATL cell lines.
(2) The 5' regulatory region of those genes were isolated from human placenta genomic library. The 2kb fragments were ligated to firefly luciferase reporter gene. After cotransfection of these plasmids with TAX, the transactivator of HTLV-1, into Jurkat cells, moderate transactivation was observed. Further identification of responsible elements or regions in the promoters is to be performed.