2019 Fiscal Year Final Research Report
Identification and functional analysis of gene aberrations in hematological malignancy with complex chromosomal abnormality using RNA-seq analysis
| Project/Area Number |
16K09860
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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 | Fujita Health University |
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Principal Investigator |
ABE AKIHIRO 藤田医科大学, 医学部, 客員准教授 (00432261)
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| Co-Investigator(Kenkyū-buntansha) |
恵美 宣彦 藤田医科大学, 医学部, 教授 (30185144)
山本 幸也 藤田医科大学, 医学部, 准教授 (90410703)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | RNA-seq / fusion gene / translocation / Leukemia / RUNX1 / G-CSF |
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| Outline of Final Research Achievements |
1. We have analyzed 48 cases of hematological malignancy using RNA-seq.
2. We have identified RUNX1-GRIK2as from relapsed/secondary acute myeloid leukemia (AML) with complex chromosomal abnormalities. This case was initially diagnosed as AML with inv(16)(p13;q22)/CBFB-MYH11 (FAB classification M4Eo). The truncated RUNX1 generated from RUNX1-GRIK2as induced the expression of the granulocyte colony-stimulating factor (G-CSF) receptor on 32D myeloid leukemia cells and enhanced proliferation in response to G-CSF. We found that several SNVs with high pathogenic scores were common in both initial and relapsed leukemia. Furthermore, the alteration of TP53 G245S occurred only at relapse.
3. We have also identified TM7SF3-VPS13B and VPS13B-RUNX1 from RUNX1-RUNX1T1-positive AML with t(8;12;21)(q22:p12;q22), ETV6-IAPP and ETV6-ABCC9 from two cases of AML with 12p abnormalities, and TCF4-MAML3 from blastic NK cell leukemia with complex chromosomal abnormalities involving t(4;18)(q31;q21).
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| Free Research Field |
血液学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、染色体核型からは推定困難な融合遺伝子を、網羅的次世代シークエンスによるRNA-seq解析を用いて同定し、複雑な染色体異常に関与する遺伝子異常を明らかにするとともに、得られた遺伝子異常の機能解析を進めるものである。今回同定した短縮型RUNX1がG-CSFへの反応性を高めること、再発時にTP53の変異が加わり複雑核型を示したことは、白血病発症機構を考える上で興味深い。また、複雑核型を有する症例は、治療困難な症例が多ため、そこに関与する遺伝子異常を明らかにすることは、新しい治療法を開発して行く上で役立つものと考える。
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