CRISPR screening for identification of molecular targets of T/NK cell lymphomas

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08313
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Hokkaido University
• Principal Investigator: Nakagawa Masao 北海道大学, 医学研究院, 助教 (80435859)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: T細胞リンパ腫 / NK細胞リンパ腫 / ATLL / CRISPR / 分子標的治療

Outline of Final Research Achievements

In this study, we performed genome-wide CRISPR-Cas9 screens in multiple T/NK lymphoma cell lines for identifying essential genes for cellular proliferation/survival in a series of T/NK cell lymphoma cell lines. Positive and negative control sgRNAs were correctly identified through the entire screening, confirming the validity of the screening results. We identified genes which were selectively essential for each diease group in T/NK cell lymphomas. Some among the essential genes were confirmed in the follow-up functional experiments. All together, we established an entire list of candidate genes for molecular targeted therapies in T/NK cell lymphomas.

Free Research Field

血液腫瘍学、分子腫瘍学、分子生物学、腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

T/NK細胞リンパ腫の多くは現行の治療に対して５年生存率３０％と予後不良である。今回の研究からT/NK細胞リンパ腫の治療標的分子・分子シグナリングの包括的リストを作成できたことで、新規分子標的治療開発が加速され、将来的にT/NK細胞リンパ腫の治療成績の向上に貢献することができる。また、T/NK細胞リンパ腫の増殖・生存の分子メカニズムの理解が進んだ点は学術的意義が高い。