Functional analysis of novel fusion gene (OFD1-JAK2) found in pediatric BCP-ALL patient

• Project/Area Number: 17K16277
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: National Center for Child Health and Development (2018); Kyoto Prefectural University of Medicine (2017)
• Principal Investigator: Sakamoto Kenichi 国立研究開発法人国立成育医療研究センター, 小児がんセンター, フェロー (20782048)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 急性リンパ性白血病 / OFD1-JAK2 / Ph-like ALL / Ph-lile ALL / チロシンキナーゼ関連融合遺伝子 / JAK2 / OFD1

Outline of Final Research Achievements

The OFD1-JAK2 forced expression Ba / F3 cells were successfully generated. However, it has not been possible to acquire IL-3 independent proliferation. The Ba / F3 cells that express another JAK2 fusion gene performed at the same time have acquired IL-3-independent growth ability, suggesting that there may be functional differences among JAK2-related fusion genes.

Academic Significance and Societal Importance of the Research Achievements

小児の急性リンパ性白血病（ALL）の中でもPh-like ALLと呼ばれる一群は化学療法抵抗性で、予後が悪いことが知られている。Ph-like ALL患者からはJAK2を含む融合遺伝子が複数同定されており、JAK2阻害剤の効果が期待されている。JAK2関連融合遺伝子は、融合遺伝子のJAK2の相手方遺伝子が多岐にわたり、ここの融合遺伝子により機能的な差異がある可能性も示唆される。