Elucidation of the factor involved in the dynamic differentiation of lymphoplasmacytic lymphoma

• Project/Area Number: 18K07068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: University of the Ryukyus (2020); Osaka City University (2019); Osaka University (2018)
• Principal Investigator: WADA Naoki 琉球大学, 医学(系)研究科(研究院), 教授 (80521731)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 悪性リンパ腫 / リンパ形質細胞性リンパ腫 / 分化動態 / グルタミン

Outline of Final Research Achievements

Glutamine (Gln) is important not only for cell proliferation but also for differentiation. Although Gln is essential for plasmacytic differentiation of lymphocytes, no study has been done on the effect of Gln on differentiation of tumor cells, such as lymphoma. Here I examined the effect of Gln on plasmacytic differentiation of lymphoplasmacytic lymphoma (LPL) with its cell line. Gln promoted plasmacytic differentiation of LPL, and p38 MAPK signaling pathway mediated such differentiation. I previously reported that the subpopulation with plasmacytic differentiation was vulnerable to apoptosis in LPL. Although it is difficult to lead these findings to the radical therapy, they might help the treatment of LPL.

Academic Significance and Societal Importance of the Research Achievements

リンパ形質細胞性リンパ腫（LPL）において、グルタミンはp38 MAPKを介して形質細胞分化を促進していることが分かった。研究代表者は、LPLにおいて、形質細胞に分化した細胞群がアポトーシスに脆弱なことを既に報告した。（Lab Invest, 2014）。従って、グルタミンは、LPLにおいて、アポトーシスに脆弱な分化した細胞群の割合を増やす因子であることが分かった。このことは抗腫瘍効果（分化誘導療法など）への活用につながる可能性があると考える。

Research Products

• [Journal Article] Effect of glutamine on lymphoplasmacytic lymphoma, especially on the viewpoint of the differentiation into vulnerable subpopulation. (2018)
  • Author(s): Wada N, Nojima S, Tahara SI, Ohshima K, Kurashige M, Kawasaki K, Tone M, Kusumoto S, Ikeda JI, Morii E.
  • Journal Title: Pathol Res Pract Volume: 214 Issue: 10 Pages: 1667-1674
  • DOI: 10.1016/j.prp.2018.08.019
  • Peer Reviewed / Open Access
• [Presentation] リンパ形質細胞性リンパ腫の分化に対してグルタミンが及ぼす効果について (2020)
  • Author(s): 和田直樹, 大畑麻衣, 田中さやか, 桑江優子, 大澤政彦, 森井英一
  • Organizer: 第109回日本病理学会総会