| Budget Amount *help |
¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Research Abstract |
We have established a refined chromosome banding technique using ethidium bromide(EBr), which enabled us more precise chromosome analyses of MDS and elucidated the consistent telation between their chromosome abnormalities and prognosis. Approximately two thirds of MDS patients had clonal chromosome abnormalities and patients with #5 and/or #7 abnormalities had poor prognosis. On the other hand, we have established a new technique using poly-L-lysine coated glass- slides to examine chromosomes of single hemopoietic colonies from patients with chronic myelogenous leukemia(CML), acute nonlymphocytic leukemia(ANLL), and myelodysplastic syndrome(MDS). In a case of CML patient, we found a blastic clone with double Ph^1 in a granulocytic colony during the chronic phase 3 months before the overt blastic crisis. In cases of ANLL patients, we have proved the clonal growth of cytogenetically abnormal progenitors from patients with t(8;21) and t(15;17) under the stimulation of HPCM or PHA-LCM. Wh
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ereas, progenitors from patients with inv(16) form colonies with a normal karyotype under the same culture condition. These findings indicate that the growth pattern of leukemic progenitors is closely related with the specific chromosome abnormalities. We observed different and variable colony growth patterns by bone marrow cells in most patients with MDS, and there was no consistent relationship between FAB classification and colony forming ability. Then we have carried out chromosome analyses on single colonies derived from CFU-GM and BFU-E in MDS patients who had karyotypic abnormalities by the direct method. In some patients, abnormal clone-derived CFU-GM formed colonies. Whereas, abnormal clones failed to form colonies in other patients. We have also found the common karyotypic abnormality in BFU-E-as well as CFU-GM-derived colonies in some patients wih MDS. These results suggest that the karyotypically abnormal clones in MDS have a wide variety of colony forming ability, and that the abnormal clones can differentiate to both granulocytic and erythroid lineages. Concerning the oxido-reductiv systems, we have found that the activities of glutathione peroxidase, the concentrations of reduced glutathione in red blood cells, and the lipid peroxide levels in plasma were significantly elevated in MDS patients. Whereas, the levels of the free radical scavengers were decreased. These data suggest that the free radical reactions may play a role in the pathogenesis of MDS. Less
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