How does aberrant B lymphocyte produce a origin of multiple myeloma cells?

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08738
• 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: Fukushima Medical University
• Principal Investigator: Sakai Akira 福島県立医科大学, 医学部, 教授 (70284221)
• Co-Investigator(Kenkyū-buntansha): 阿部 悠 福島県立医科大学, 医学部, 助教 (00722472) ; 津山 尚宏 福島県立医科大学, 医学部, 准教授 (10335747)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 成熟Bリンパ球 / 多発性骨髄腫 / iPS細胞 / 再プログラミング / 形質転換

Outline of Final Research Achievements

The onset of MM is often caused by a reciprocal chromosomal translocation (cTr) between chr 14 with IgH and chr 11 with CCND1. We propose that mature B cells gain potential to transform by reprograming, and then chromosomal aberrations cause the development of abnormal B cells as a myeloma-initiating cell during B cell redifferentiation. To study myeloma-initiating cells, we have already established normal B cell-derived induced pluripotent stem cells (BiPSCs). Here we established two BiPSCs with reciprocal cTr t(11;14) using the CRISPR/Cas9 system. Furthermore, p53 was deleted using the CRISPR/Cas9 system in BiPSC13 with t(11;14). These BiPSCs differentiated into hematopoietic progenitor cells (HPCs). However, unlike cord blood, those HPCs did not differentiated into B lymphocytes by co-culture with BM stromal cell. Therefore, further ingenuity is required to differentiate those BiPSCs-derived HPCs into B lymphocytes.

Free Research Field

血液および腫瘍内科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、多発性骨髄腫 (MM) の腫瘍起源となる異常Bリンパ球は、成熟Bリンパ球が再プログラミングによってポテンシャルを獲得し染色体異常を生じた細胞であることの検証を行う。確認できれば、生体内で加齢や慢性炎症による正常細胞のエピジェネティックな変化が細胞のがん化に繋がる機序の１つであることを支持する腫瘍化のモデルであり、がん発生の予防方法の開発に繋がる。