Scholarlink

<p>Multiple myeloma (MM) is the second most frequently diagnosed malignant hematological disease. It is characterized by uncontrolled proliferation of abnormal plasma cells in the bone marrow, production of a&#xa0;monoclonal protein, and development of end-organ damage. It is typically preceded by an asymptomatic stage marked by a&#xa0;lower number of plasma cells in the bone marrow and the presence of a&#xa0;monoclonal protein in serum but without end-organ damage. Although the exact pathogenesis of MM remains unclear, early changes in the cell cycle, such as dysregulation of cyclin&#xa0;D genes in B-cells during the germinal center reaction play a&#xa0;key role in malignant transformation. Common cytogenetic abnormalities include hyperdiploidy of odd-numbered chromosomes and translocations affecting the immunoglobulin heavy chain locus. These genetic alterations can already be found in premalignant plasma cells in individuals with monoclonal gammopathy of undetermined significance (MGUS). The molecular heterogeneity of MM is evident in the diversity of mutations, with frequent involvement of genes in the NFKB and MAPK signaling pathways. Epigenetic changes, such as overexpression of the H3K36 methyltransferase <i>MMSET</i>, as well as alterations at the posttranslational level including, among other things, the ubiquitin proteasome system also contribute to pathogenesis and maintenance. Additionally, the tumor microenvironment plays a&#xa0;crucial role in the survival of MM cells and the development of resistance to treatment. An increased understanding of MM pathogenesis offers potential for new targeted treatments, particularly for high-risk MM patients.</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

Pathophysiologie des multiplen Myeloms

  • 期刊论文

  • 发表日期：

    2025年1月14日

查看全文
  • Johannes Jung,
  • Katharina Nickel,
  • Marion Högner,
  • Florian Bassermann

摘要

Multiple myeloma (MM) is the second most frequently diagnosed malignant hematological disease. It is characterized by uncontrolled proliferation of abnormal plasma cells in the bone marrow, production of a monoclonal protein, and development of end-organ damage. It is typically preceded by an asymptomatic stage marked by a lower number of plasma cells in the bone marrow and the presence of a monoclonal protein in serum but without end-organ damage. Although the exact pathogenesis of MM remains unclear, early changes in the cell cycle, such as dysregulation of cyclin D genes in B-cells during the germinal center reaction play a key role in malignant transformation. Common cytogenetic abnormalities include hyperdiploidy of odd-numbered chromosomes and translocations affecting the immunoglobulin heavy chain locus. These genetic alterations can already be found in premalignant plasma cells in individuals with monoclonal gammopathy of undetermined significance (MGUS). The molecular heterogeneity of MM is evident in the diversity of mutations, with frequent involvement of genes in the NFKB and MAPK signaling pathways. Epigenetic changes, such as overexpression of the H3K36 methyltransferase MMSET, as well as alterations at the posttranslational level including, among other things, the ubiquitin proteasome system also contribute to pathogenesis and maintenance. Additionally, the tumor microenvironment plays a crucial role in the survival of MM cells and the development of resistance to treatment. An increased understanding of MM pathogenesis offers potential for new targeted treatments, particularly for high-risk MM patients.