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<p>Multiple myeloma progresses from bone marrow–confined disease to systemic forms through processes linked to loss of adhesion and EMT-related programs. We analyzed baseline plasma cell RNA-seq, microarray, and single-cell datasets to derive and validate a dissemination score. In the newly diagnosed MMRF CoMMpass cohort (<i>n</i> = 754), differential expression analyses of circulating plasma cells (<i>n</i> = 592) and PET-CT–confirmed plasmacytomas (<i>n</i> = 118), integrated with 1114 EMTome genes, identified 1357 dissemination-associated genes. Elastic Net Cox regression derived a 30-gene Dissemination Score (DS) that stratified overall survival (54.5 vs 102.5 mo; C-index 0.71) and improved prognostic performance when added to UAMS70 and EMC92 in bootstrap analyses. DS was associated with Adverse stromal interaction (ASI) and stratified high-risk ASI interactions. In an independent Mayo Clinic cohort (<i>n</i> = 133), DS reproduced prognostic discrimination (52.1 vs 113.6 mo, <i>p</i> &lt; 0.01) and predicted earlier dissemination events (2.1 vs 6.8 yrs, <i>p</i> &lt; 0.01). In GSE117156, circulating plasma cells showed consistently higher DS than marrow plasma cells across MGUS, SMM, MM, and AL, with progressive DS increase from controls to MM. In GSE106218, CD138⁺ extramedullary plasma cells had higher DS than marrow plasma cells (<i>p</i> &lt; 0.01). Collectively, DS quantifies dissemination biology.</p>

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Gene expression-based dissemination score predicts early spread and poor outcomes in multiple myeloma

  • 期刊论文

  • 发表日期：

    2026年4月22日

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  • Arwa Bohra,
  • Surendra Dasari,
  • Saurabh Zanwar,
  • Wilson I. Gonsalves,
  • Prashant Kapoor,
  • Moritz Binder,
  • Angela Dispenzieri,
  • Michael M. Timm,
  • Francis Buadi,
  • Dragan Jevremovic,
  • S. Vincent Rajkumar,
  • Shaji Kumar

摘要

Multiple myeloma progresses from bone marrow–confined disease to systemic forms through processes linked to loss of adhesion and EMT-related programs. We analyzed baseline plasma cell RNA-seq, microarray, and single-cell datasets to derive and validate a dissemination score. In the newly diagnosed MMRF CoMMpass cohort (n = 754), differential expression analyses of circulating plasma cells (n = 592) and PET-CT–confirmed plasmacytomas (n = 118), integrated with 1114 EMTome genes, identified 1357 dissemination-associated genes. Elastic Net Cox regression derived a 30-gene Dissemination Score (DS) that stratified overall survival (54.5 vs 102.5 mo; C-index 0.71) and improved prognostic performance when added to UAMS70 and EMC92 in bootstrap analyses. DS was associated with Adverse stromal interaction (ASI) and stratified high-risk ASI interactions. In an independent Mayo Clinic cohort (n = 133), DS reproduced prognostic discrimination (52.1 vs 113.6 mo, p < 0.01) and predicted earlier dissemination events (2.1 vs 6.8 yrs, p < 0.01). In GSE117156, circulating plasma cells showed consistently higher DS than marrow plasma cells across MGUS, SMM, MM, and AL, with progressive DS increase from controls to MM. In GSE106218, CD138⁺ extramedullary plasma cells had higher DS than marrow plasma cells (p < 0.01). Collectively, DS quantifies dissemination biology.