Reprogramming technology revealed the genetic and functional diversity present in an individual myelodysplastic syndrome patient
| Project/Area Number |
16K09847
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Research Collaborator |
Yoshida Yoshinori
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 骨髄異形成症候群 / 二次性急性骨髄性白血病 / リプログラミング / iPS細胞 / 腫瘍内多様性 / 新規治療薬 |
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| Outline of Final Research Achievements |
We successfully generated multiple iPS cell lines from abnormal clones of patients with myelodysplastic syndromes or secondary AML (MDS/sAML) evolved from MDS. Hematopoietic progenitor cells (HPCs) differentiated from MDS-derived MDS-iPS cell lines showed decreased colony formation, whereas HPCs differentiated from sAML-derived MDS-iPS cell lines showed increased colony formation, compared with isogenic normal iPS cell lines, and induced lethal AML in transplanted immunodeficient mice. Next, we performed whole-exome analysis to find that some of the somatic mutations detected in bulk cells of MDS/sAML patients are shared in MDS-iPS cell lines but not in isogenic normal iPS cell lines. Furthermore, we performed coprehensive gene expression analysis in hematopoietic progenitor cells differentiated from MDS-iPS cell lines and isogenic normal iPS cell lines, identifying disease-specific expression change.
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| Academic Significance and Societal Importance of the Research Achievements |
予後不良のクローン性造血障害であるMDS/sAMLには病態を再現し解析するモデルが殆どなく、治療法の開発を可能にするツールが殆どないのが現状である。我々は患者から樹立した複数のMDS-iPS細胞株の網羅的ゲノム解析と、MDS-iPS細胞から再誘導された造血前駆細胞の分化能・造腫瘍能などの機能解析を組み合わせることにより、MDS/sAMLの腫瘍内多様性及び発症・進展機構を明らかした。
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Report
(4 results)
Research Products
(8 results)
