Novel therapeutic approaches for treatment of myeloproliferative neoplasms based on aging control

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08358
• 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: Yamaguchi University
• Principal Investigator: Yujiri Toshiaki 山口大学, 大学院医学系研究科, 教授 (80346551)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 骨髄増殖性腫瘍 / 細胞老化

Outline of Final Research Achievements

Myeloproliferative neoplasms (MPN) are often characterized by specific somatic mutations: JAK2, CALR, or MPL. A single nucleotide polymorphism (SNP), rs2736100, in the reverse transcriptase gene (TERT) and a germline JAK2 46/1 haplotype(46/1) have been associated with MPN in North American and European patients. We examined 201 Japanese MPN patients, as well as 366 control individuals for TERT rs2736100 and JAK2 rs10974944, a tagging SNP of the 46/1. Correlations between the JAK2 V617F allele burden and TERT rs2736100 or JAK2 rs10974944 were evaluated using a digital PCR assay. The 46/1, but not the TERT rs2736100, was correlated to the JAK2 V617F mutant allele burden in JAK2 V617F-positive MPN patients. In conclusion, we demonstrated that both TERT rs2736100_C and 46/1 are predisposing factors for MPNs in Japanese patients. While TERT rs2736100_C tended to have a more general, non-specific effect on all MPNs, the 46/1 was essentially predisposed to the JAK2 V617F-positive MPNs.

Free Research Field

造血器腫瘍

Academic Significance and Societal Importance of the Research Achievements

骨髄増殖性腫瘍は高齢者によく認められる疾患である。一般的には経過の緩徐な疾患であるが、脳心血管疾患リスクは高くなり生活の質が低下する。さらに二次性骨髄線維症や急性骨髄性白血病への病勢進行に加え、他の固形癌の発症も問題になる。今回の我々の研究では遺伝的背景(TERT遺伝子多型）に起因する骨髄増殖性腫瘍に加え、他の固形癌のリスク因子となるが日本人患者でも明らかになった。今後、高齢患者の増加に伴い重複癌患者の増加が推測されていることから重要な情報となる事が考えられる。また血管リスク因子を遺伝的背景から同定することができれば、さらに有用な情報となり得る。