CRLF2 over-expression analysis in precursor B-cell acute lymphoblastic leukemia in children

• Project/Area Number: 15K19620
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tokyo Medical and Dental University (2016-2018); The University of Tokushima (2015)
• Principal Investigator: NARUTO TAKUYA 東京医科歯科大学, 大学院医歯学総合研究科, プロジェクト助教 (60438124)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: CRLF2 / 小児急性リンパ性白血病

Outline of Final Research Achievements

Childhood acute lymphoblastic leukemia (ALL) has significantly improved treatment results with recent stratification treatments. However, about 20% of cases relapse, and there are cases without recurrence of known poor prognosis factors (Philadelphia chromosome). We established two ALL cell lines with JAK2 gene mutation and high expression of CRLF2. These two strains have acquired extremely strong resistance to anticancer drugs and oxidative stress. CRLF2 also acts as a TSLP receptor and is thought to signal through the JAK-STAT pathway. In this study, we performed functional analysis centering on JAK2, and it was suggested that TLSP receptor cooperates in CRLF2 expression cell to promote malignant transformation.

Academic Significance and Societal Importance of the Research Achievements

小児の急性リンパ性白血病は小児がんの約 40%を占める大きなグループであり、近年の層別化治療により治療成績は大幅に向上している。しかしなお約 20%の症例で再発がみられ、その再発例では既存の予後不良因子を持たない例も存在する。遺伝子異常により遺伝子再構成を伴うCRLF2が高い発現を示しているタイプで、患者のリンパ球から樹立した細胞株を研究に用いた。シグナル伝達経路に対する阻害薬の効果等を検討し、治療層別化因子としての基礎データを提供した。