Scholarlink

<p>The increasing therapeutic options for multiple myeloma (MM) have significantly improved long-term survival for many patients. However, disease progression remains inevitable due to the emergence of drug-resistant myeloma cell populations, often culminating in extramedullary disease manifestations. In this study, we identified CD70-expressing myeloma cells as critical drivers of disease progression and propagation. CD70 expression in MM cells is an independent negative prognostic factor for overall survival. Mechanistically, CD70/CD27 signaling activates the MAPK/ERK and Wnt signaling pathways in MM cell lines and primary patient-derived MM samples, promoting increased cell cycling and proliferation. This proliferative advantage results in elevated CD70 expression in advanced MM stages, particularly in extramedullary myeloma. Functional inhibition of CD70/CD27 signaling, achieved either by generating CD70-knockout primary MM cells or with blocking monoclonal antibodies, completely abrogated tumor growth in xenotransplantation models. Furthermore, the ADCC-enhanced anti-CD70 antibody, cusatuzumab, demonstrated high efficacy in treating myeloma in xenotransplantation&#xa0;models. Collectively, these findings underscore the critical role of CD70/CD27 signaling in activating MAPK/ERK and Wnt pathways essential for MM progression. Targeting CD70 with blocking or ADCC-enhanced antibodies represents a promising therapeutic strategy, particularly for advanced MM stages characterized by high CD70 expression.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

CD70/CD27 signaling promotes the pathogenesis of multiple myeloma and represents a promising therapeutic target

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月23日

查看全文
  • Stefan Forster,
  • Chantal Reinhardt,
  • Maxime Boy,
  • Adrian Wegmüller,
  • Alessio Hinrichsen,
  • Christian M. Schürch,
  • Frido K. Brühl,
  • Falko Fend,
  • Alexandar Tzankov,
  • Marie-Noëlle Kronig,
  • Michaela Römmele,
  • Angéline Glück,
  • Benjamin Lüscher,
  • Myriam Legros,
  • Ulrike Bacher,
  • Katja Seipel,
  • Thomas Pabst,
  • Ramin Radpour,
  • Carsten Riether,
  • Adrian F. Ochsenbein

摘要

The increasing therapeutic options for multiple myeloma (MM) have significantly improved long-term survival for many patients. However, disease progression remains inevitable due to the emergence of drug-resistant myeloma cell populations, often culminating in extramedullary disease manifestations. In this study, we identified CD70-expressing myeloma cells as critical drivers of disease progression and propagation. CD70 expression in MM cells is an independent negative prognostic factor for overall survival. Mechanistically, CD70/CD27 signaling activates the MAPK/ERK and Wnt signaling pathways in MM cell lines and primary patient-derived MM samples, promoting increased cell cycling and proliferation. This proliferative advantage results in elevated CD70 expression in advanced MM stages, particularly in extramedullary myeloma. Functional inhibition of CD70/CD27 signaling, achieved either by generating CD70-knockout primary MM cells or with blocking monoclonal antibodies, completely abrogated tumor growth in xenotransplantation models. Furthermore, the ADCC-enhanced anti-CD70 antibody, cusatuzumab, demonstrated high efficacy in treating myeloma in xenotransplantation models. Collectively, these findings underscore the critical role of CD70/CD27 signaling in activating MAPK/ERK and Wnt pathways essential for MM progression. Targeting CD70 with blocking or ADCC-enhanced antibodies represents a promising therapeutic strategy, particularly for advanced MM stages characterized by high CD70 expression.