Study on the Significance of Dexamethasone in Lymphoid Malignancies

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20848
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Teikyo University
• Principal Investigator: Shirasaki Ryosuke 帝京大学, 医学部, 講師 (40569133)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: EOL1 / 慢性好酸球性白血病 / Lymphoma / RAJI

Outline of Final Research Achievements

Steroids are utilized as anticancer agents in various diseases, excluding myeloid leukemia. However, the exact mechanism of steroids as anticancer agents remains unclear. In this study, our objective was to identify the cell-killing effects of dexamethasone through a Genome-scale CRISPR activation screen. We conducted experiments using RAJI cells, a lymphoma cell line, and EOL-1 cells, a cell line derived from CEL. The results revealed a gene cluster including BCL2L11 as a proliferative factor in RAJI cells, whereas a gene cluster including PLAUR was identified in EOL-1 cells. Furthermore, dexamethasone treatment led to the identification of a gene cluster containing USP17L19 as a resistance factor in RAJI cells.

Free Research Field

Biology of cancer

Academic Significance and Societal Importance of the Research Achievements

今回発見した遺伝子群はこれら白血病に対する増殖因子であり、現在までに報告されていないものがほとんどである。特に好酸球性白血病細胞を使用したCRISPR activation screeningでは上記PLAURの他に好酸球の分化に関わる遺伝子群を新たに発見し、更にこの実験が正しいと証左に足る増殖因子として喘息において重要なサイトカインであるIL33が増殖因子となる事も判明した。また、RAJI細胞におけるDexamethasone耐性因子としてユビキチン化阻害タンパクのUSP17L19が見つかりこの経路の阻害がDexamethasone感受性を上げる可能性がある。