Identification of T cell pathway causing the acquired aplastic anemia

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16184
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kanazawa University
• Principal Investigator: Hosokawa Kohei 金沢大学, 附属病院, 助教 (10786239)
• Research Collaborator: Hosomichi Kazuyoshi ; Young Neal. S.
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 再生不良性貧血 / トランスクリプトーム解析 / 造血不全

Outline of Final Research Achievements

To identify aberrant molecular mechanisms involved in immune targeting of hematopoietic stem cells in bone marrow, we applied RNA-seq to examine the transcriptome of T cell subsets from AA/PNH patients and healthy control subjects. Differentially expressed gene analysis in four different T cell subsets from PNH and healthy control subjects showed distinct transcriptional profiles, depending on the T cell subsets. By pathway analysis, we identified novel signaling pathways in T cell subsets, including increased gene expression involved in TNFR, IGF1, NOTCH, AP-1, and ATF2 pathways. Dysregulation of several candidate genes (JUN, TNFAIP3, TOB1, GIMAP4, GIMAP6, TRMT112, NR4A2, CD69, and TNFSF8) was validated by quantitative real-time RT-PCR and flow cytometry.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

骨髄不全型PNHにおいてT細胞を正または負に制御するパスウェイや遺伝子が同定されたことから、これらの遺伝子を標的とした治療への応用が期待される。