| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Aplastic anemia is a intractable disease presenting with immune-mediated marrow injury, complication of both myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML), and evolution of mutant clones including paroxysmal nocturnal hemoglobinuria (PNH) clones that harbor somatic mutation of PIG-A gene. As mutant clones are also frequently observed in both PNH and MDS, a common mechanism of evolution of the clones may exist among these disorders. We have reported that a mutable condition of hematopoietic cells in PNH by measurement of mutation frequency of hypoxanthine guanine phosphoribosyl transferase (HPRT) gene. As considered the close relationship among these diseases, it is supposed existence of the mutable condition in both aplastic anemia and MDS. On the other hand, aplastic anemia showed an remarkable improvement of the survival by immuno-suppressive therapy. According to the improvement, clonal complication manifest such as PNH, MDS and leukemia. Then, the mechanism o
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f the evolution of mutant clones in the diseases is to be clarified. To clarify the mutable condition, we planned the measurement of the mutation frequency of HPRT gene among both aplastic anemia and MDS. Peripheral T-cells were purified by density gradient methods and cultured under a condition containing 6-thioguanine to grow colonies consisting of the HPRT mutant cells. Among 5 cases of aplastic anemia, no case showed the colony formation. As the peripheral T-cells, bone marrow-progenitor cells also showed the extremely low frequency of the colony formation. In MDS, the colony formation of both peripheral T-cells and bone-marrow cells were not detected as aplastic anemia. Because of the lower frequency of the colony formation compared to PNH, the mutation frequency could not be calculated. We therefore conclude that the unknown factors may deficient in capability to form colony under the condition of 6-thioguanine than in PNH. This may indicate the marrow-injury in both aplastic anemia and MDS. Less
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