2022 Fiscal Year Final Research Report

Understanding the mechanism of cell tumorigenesis promoted by essential thrombocythemia specific transcriptional network

Research Project

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Project/Area Number	20H03715
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 54010:Hematology and medical oncology-related
Research Institution	Juntendo University
Principal Investigator	Komatsu Norio 順天堂大学, 医学部, 特任教授 (50186798)
Co-Investigator(Kenkyū-buntansha)	森下総司順天堂大学, 医学部, 特任助教 (10635866) 今井美沙順天堂大学, 大学院医学研究科, 非常勤助教 (50709003) 荒木真理人順天堂大学, 大学院医学研究科, 客員教授 (80613843)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	骨髄増殖性腫瘍 / 小胞体ストレス応答因子 / 本態性血小板血症 / 血小板 / 巨核球
Outline of Final Research Achievements	Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are a group of hematopoietic malignancies in which somatic mutations occur in hematopoietic stem/progenitor cells, resulting in an abnormal increase in blood cells and fibrosis of the bone marrow. In this study, we analyzed the clinical significance of the CREB3L1 gene, which specifically expresses on platelets derived from patients with MPNs, and its impact on the development of MPNs. Analysis of platelet-derived RNA from patients with MPNs suggested that the CREB3L1 gene may be a clinically valuable gene that can be used not only for the diagnosis but also for prognosis prediction of MPNs. Furthermore, a series of analyses using CD34-positive cells isolated from the peripheral blood of patients with MPNs demonstrated that the CREB3L1 gene is required for tumor cell differentiation and survival in MPNs.
Free Research Field	血液学
Academic Significance and Societal Importance of the Research Achievements	本研究では，血液学的に前例のないCREB3L1遺伝子の高発現が，MPNs発症にどう関与するかを明らかにしたことが，学術的に意義のある点である。さらに，CREB3L1の発現がMPNsの診断や予後予測に有用である可能性を示し，CREB3L1の発現を抑制すると腫瘍細胞が死滅することを明らかにしたことから，CREB3L1がMPNsにおける新たな診断マーカーや治療標的ともなり得るため，臨床的にも非常に価値があると考えられる。