| Co-Investigator(Kenkyū-buntansha) |
TANAKA Kimio Hiroshima Univ., Res.Inst.Nuclear Med. & Biol., Research Associate, 原爆放射能医学研究所, 助手 (70116622)
NIWA Ohtura Hiroshima Univ., Res.Inst.Nuclear Med. & Biol., Associate Professor, 原爆放射能医学研究所, 助教授 (80093293)
KAMADA Nanao Hiroshima Univ., Res.Inst.Nuclear Med. & Biol., Professor, 原爆放射能医学研究所, 教授 (00034629)
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| Budget Amount *help |
¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1989: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1988: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Research Abstract |
It has been known that the cells of some chronic hematopoietic malignancies, such as chronic myelogenous leukemia(CML), myelodysplastic syndromes(MDS), polycythemia vera(PV), myelofibrobrosis (MMM) and essential thrombocythemia(ET), acquire the abrupt growth advantage after some periods.
It has been known that the cells of aome chronic hematopoietic malignancies, such as chronic myelogenous leukemia(CML), myelodysplastic syndromes(MDS), polycythemia vera(PV), myelofibrobrosis(MMM) and essential thrombocythemia(ET), acquire the abrupt growth advantage after some periods. However little is known about the mechanism of the evolution. We studied to clarify such a mechanism from the cytofenetic and molecular aspects. They consisted of CML(145 cases), MDS(54 cases), PV(9 cases), MMM(4 cases) and ET(5 cases). A complex Ph^1 translocation and a masked Ph^1 translocation other than standard Ph^1 translocation were observed in 9 of CML cases. Eight of 11 cases who evolved to blastic crisis had ad
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ditional chromosomal abnormalities other than Ph^1 chromosome. Twenty four of 54 cases with MDS showed chromosomal abnormalities. Interestingly, -7, +der(1)t(1;7)(p11;p11) was detected in 2 cases, one is acute leukemia evoluted from PV, the other is evoluted from aplastic anemia. Neither chromosomal abnormalities nor clinical change was observed in MMM and ET. We attempted to analysis the molecular basis in order to better understanding of the role of Ph^1 chromosome in 90 cases with CML. Southern blot analysis revealed that the breakage occurred outside the bcr(break point cluster region) in two cases(2%). A deletion of 3' side bcr in 9 cases(10%) and a deletion of 5' side bcr in 2 cases(2%) were also demonstrated chimeric bcr-abl gene expression was observed by PCR(polymerase chain reaction) method in cases which Northern blot analysis could fail to detect. Both cases who had a deletion of 5' side bcr represented a lymphoid crisis. Ph^1 chromosome and bcr rearrangement were disappeared after Interferron therapy, but still rearrangement was detected by PCR method. These findings suggest that the utility of the cytogenetic and molecular examination for identifying the genetic events involving in the pathogenesis of chronic hematopoietic malignancies and its evolution. Less
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