| Project/Area Number |
15590996
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SATO Noriharu The University of Tokyo, Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (90162461)
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| Co-Investigator(Kenkyū-buntansha) |
TOJO Arinobu The University of Tokyo, Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (00211681)
TAKAHASHI Satoshi The University of Tokyo, Institute of Medical Science, Assistant Professor, 医科学研究所, 講師 (60226834)
ISEKI Tohru Chiba University, Department of Blood transfusion, Assistant Professor, 医学部附属病院・輸血部, 講師 (10232365)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Cord Blood / Transplantation / GVHD / GVL / MICB / CML / 臍帯血幹細胞移植 / 血液疾患 / NK細胞 / 発現解析 / 遺伝子多型 |
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| Research Abstract |
We started the study on GVHD and GVL in cord blood transplantation for adult patients with hematological malignancies. Cord blood transplantation was initially performed mainly in children but accumulating evidence indicates that cord blood transplantation could be safely used in adult patients. Although most cord blood transplantations have been performed in the 2-locus-mismatch settings, this procedure has unexpectedly resulted in higher engraftment efficiency and lower rates of severe GVHD. We aimed to uncover molecular mechanisms underlying excellent results in cord blood transplantation for adults.
Cells mainly containing CD8+, CD56+, CD4+ and CD14+population were separately collected from recipients when they were suffering from GVHD or when they recovered from the GVHD, and were analyzed for approximately 600 genes. Thus far, we have not obtained consistent findings. In parallel with this, we examined new polymorphisms in the promoter of immune related genes. We found deletion/insertion polymorphism in the promoter of IL-2Rα gene (-1022_-1021delTG) (dbSNPss#28448139).
Recently NK cells are found important for tumor eradication from hosts. NK cells use activating receptors to kill tumor cells. These include NKG2D, KIR, NKp30, NKp44, NKp46. MICB is a ligand for NKG2D and is reported to be expressed on leukemia cells. We also examined MICB genotypes in patients and controls and found MICB0104 is statistically associated with CML. This may reflect natural GVL effect of NK cells against leukemogenesis.
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