Finding poor prognostic factors of myelofibrosis targeting tumor cell population

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19203
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Juntendo University
• Principal Investigator: Morishita Soji 順天堂大学, 医学部, 助教 (10635866)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 予後不良因子 / 骨髄線維症 / 骨髄増殖生腫瘍 / ターゲットリシーケンシング

Outline of Final Research Achievements

The prognosis of primary myelofibrosis (PMF) is poor in comparison to that of other subtypes of myeloproliferative neoplasms. To investigate the relationship between mutations and prognosis of PMF, a massively parallel target sequencing identifying mutations on 72 regions locating at MPNs-relevant 14 genes (CSF3R, MPL, JAK2, CALR, DNMT3A, TET2, EZH2, ASXL1, IDH1/2, SRSF2, SF3B1, U2AF1, and TP53) have designed and the mutation spectrum of 101 Japanese patients having overt or prefibrotic PMF diagnosed by WHO 2016 criteria. As a result, 66 out of 101 PMF patients (65.3%) harbored any mutations other than JAK2, CALR, or MPL mutations. In the 66 patients, ASXL1 mutations were the most frequently detected (42.6%). The prognostic risk classification based on the combination of CALR and ASXL1 mutation revealed that the CALR-/ASXL1+ group had significantly higher mutation load (P<.001). We also clarified that SRSF2 mutations strongly associated to the highly risks predicted by DIPSS (P<.05).

Free Research Field

病態検査医学

Academic Significance and Societal Importance of the Research Achievements

本研究では，これまでの報告と同様，ASXL1変異とSRSF2変異が骨髄線維症の予後不良因子である可能性が示唆された。実際にこれらの遺伝子変異を有する症例における予後を詳らかにする必要はあるものの，将来的には，事前にこれらの遺伝子変異の有無を調べることで，骨髄移植など，より積極的な治療を選択できるようになると考えられ，社会的意義は大きいと言える。