| Project/Area Number |
62570289
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Legal medicine
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| Research Institution | Ehime university |
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Principal Investigator |
SHIOSAKA Takahiko Ehime University, Associate proefessor, 医学部, 助教授 (90035486)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Leukaemia / Chronic Lymphocytic Leukaemia / cDNA Library / gene expression / HL-60 / oncogene / c-myc / TPA / cDNAlibrary / cDNA / library |
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| Research Abstract |
Tortal cellular RNAs a variety of hematopoietic neoplastic cells and normal lymphocytes werte analyzed for homology with 21 recombinant DNA segments complementary to the specific mRNA of cells from a patient with chronic lymphocytic leukemia. Twenty of the clones(except for clone 8-6G) were not significantly represented in the mRNA from normal lymphocytes. The relative concentration of three clones(6-1E,7-3G and 9-5C) in the RNAs from a variety of normal and leukemic leukocytes and human hematopoietic cell lines were measured by Northern blot hybridization. This showed that 7-3G,6-1E and 9-5C RNA were highly abundant in RNA from hematopoietic neoplastic leukocytes.
Expression of these three clones was studied by nucleic acid hybridization in human promyelocytic leukaemia cells (HL-60)treated with chemical inducers of cell differentiation and in primary cells derived from 27 patients with leukaemia or myerodysplastic syndrome. The diffrerentiation of HL-60 cells into macrophage like cells upon induction by 12-o-tetradecanoyl-phorbol-13-acetate(TPA) was accomanied by rapid induction of the expressin of 6-1E nad 7-3G genes.
The expression of the 6-1E and /or 7-3G gen was induced by TPA in foyr of 6 samples derived from patients who achieved complete remission, but not in any of the acute nonlymphocytic leukaemia samples from patients who failed to achieve complete remission. These findings suggest that expression of the 6-1E and 7-3G genes is related to macrophage-monocytic differentiation and that alternation of these gene expression in fresh leukaemia cells after one hour of TPA treatment a re of prognostic significance in predicting the responce to therapy.
Futhermore, we have shown that different oncogenes(c-myc,c-abl,c-fos and c-Ha -ras) are expressed in different leukaemic types and that alteration of oncogen e expression after addition of TPA varies from one type of leukaemia to another and within a given individual leukaemic type.
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