Elucidation of the high-grade pathogenesis of universal mature B cell tumor model by using comprehensive gene editing

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16274
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Mizutani Shinsuke 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40883088)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: B細胞性リンパ腫 / 多発性骨髄腫 / PDPK1 / RSK2

Outline of Final Research Achievements

B cell lymphoma (BCL) and multiple myeloma (MM) are highly prevalent hematopoietic tumors, and overcoming refractory cases remains an important challenge. In this study, we generated "BCL disease-cross-sectional and universal model cells" by inducing PDPK1-RSK2 signaling homeostatic activation in an immortalized human normal B cell-derived cell line, and performed a comprehensive screening of human whole genome CRISPR/Cas9 gene knockout against these cells to identify cells with high tumorigenicity, resistance to cell death stimulation, chromosomal and genetic instability We are in the process of identifying molecular abnormalities that induce high tumorigenicity, resistance to cell death stimulation, chromosomal and genetic instability, and anti-tumor cell immune evasion mechanisms.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究でBCL、MMにおけるPDPK1-RSK2シグナルの恒常的活性化の病型横断的・普遍的な病態形成する「がん抑制遺伝子、がん遺伝子」が同定できれば、染色体・遺伝子不安定性獲得によるクローン性進化、骨髄由来抑制系細胞誘導機序等の解明に繋がり、一部の症例に認める高度治療抵抗性獲得病態を司る付加的分子異常の解明と克服に大きな一歩となるだけでなく、他のがん種に関する応用研究も期待できる。