Mutational profiles of T cells in bone marrro failure syndrome as clinical markers

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08709
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Shinshu University
• Principal Investigator: Ishida Fumihiro 信州大学, 学術研究院保健学系, 教授 (80311695)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 赤芽球癆 / 遺伝子変異 / 貧血 / クローン性造血

Outline of Final Research Achievements

Bone marrow failure syndrome (BMF) is defined as chronic cytopenia due to acquired impaired hematopoiesis. Cellular immune dysfunction has been a main cause of BMF, especially in aplastic anemia (AA) and pure red cell aplasia (PRCA), although the details are still uncertain.
We performed whole exome sequencing anaysis and target sequencing on peripheral blood from patients with PRCA in order to elucidate molecular pathophysiology of BMF including PRCA. In addition to well recognized STAT3 mutations, a set of genes, including clonal hematopoiesis-related genes such as epigenetic modifier genes, were frequently mutated in PRCA, which were with a different pattern from AA. Several gene mutations were associated with specific subtypes of PRCA and/or relapse after immunosuppressive therapies.
Mutational gene analyses in PRCA would be helpful for establishing better classification and diagnostic criteria of BMF including PRCA and also for clinical decision making on PRCA.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

骨髄不全症候群は後天性に造血が障害されて貧血などの血球減少を呈し慢性に経過し、しばしば難治性である。骨髄不全症候群の多くは赤芽球癆を含め厚生労働省の指定難病に指定されている。赤芽球癆には多くの病型があり、初期治療で免疫抑制療法が奏効するものの、再燃や不応例も一定の割合で生じている。今回の研究により、赤芽球癆の遺伝子変異像を特定したことで赤芽球癆の病態のより深い理解につながり、赤芽球癆を含めた骨髄不全症候群の適切な診断や病型分類に役立てることができる。また、赤芽球癆の初期治療およびその後の治療法を選択に有用である可能性がある。