2022 Fiscal Year Final Research Report
The relevance of human leukocyte antigen in the development and progression of latently infected virus-associated lymphoid malignancies.
Project/Area Number |
17K09934
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | University of the Ryukyus |
Principal Investigator |
Morishima Satoko 琉球大学, 医学(系)研究科(研究院), 准教授 (40463195)
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Co-Investigator(Kenkyū-buntansha) |
益崎 裕章 琉球大学, 医学(系)研究科(研究院), 教授 (00291899)
玉城 啓太 琉球大学, 医学(系)研究科(研究院), 客員研究員 (40806452)
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Project Period (FY) |
2017-04-01 – 2023-03-31
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Keywords | HLA / 潜伏感染ウイルス / リンパ系腫瘍 / 成人T細胞白血病リンパ腫 |
Outline of Final Research Achievements |
Human leukocyte antigen (HLA) plays a critical role in the immune response, and reduced expression of HLA is associated with poor prognosis in various types of cancers. We explored the relevance of HLA in the pathogenesis and progression of adult T-cell leukemia lymphoma (ATL). Using a next-generation sequencing (NGS)-based high-resolution HLA DNA typing method, which successfully covers the entire region of HLA genes, we analyzed eight classical HLA loci in 25 pairs of ATL and non-ATL cells from the same patients. Multiple HLA gene alterations were concurrently observed in ATL cells within the same patients, possibly reducing cell-surface expression of HLA class I molecules. In contrast, no HLA alterations were detected in five patients with chronic-type ATL. HLA alterations were associated with aggressive phenotypes, raising a possibility that ATL cells can develop immune escape mechanisms through a variety of acquired alterations in HLA genes.
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Free Research Field |
血液内科
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Academic Significance and Societal Importance of the Research Achievements |
Long-range法を用いることでATL細胞に生じるHLA遺伝子異常の特徴を明らかにすることができた。従来のHLAタイピング法では検出されないイントロンや多型に富むエクソン以外にも遺伝子異常を認め、がん細胞に生じるHLA遺伝子異常を正確に検出するためにはlong-range法を用いることが重要であることを示した。 ATLの急性型ではHLAの遺伝子異常を獲得しやすい可能性があり、ATLに対して同種移植やワクチン療法などを実施する際に、本解析によって得られる結果は治療効果を予測する上で重要な情報となる可能性がある。
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