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<p>Secondary central nervous system involvement (sCNSi) is a fatal complication of diffuse large B-cell lymphoma (DLBCL), yet its molecular determinants remain poorly understood. To investigate the mechanisms underlying CNS-preferential dissemination, we established an in vivo DLBCL xenograft model using two representative cell lines, OCI-LY19 and Toledo, followed by transcriptomic profiling of lymphoma cells isolated from the brain, peripheral organs, and parental cultures. Transcriptomic analyses revealed gene signatures associated with CNS-preferential dissemination, which were further evaluated in RNA-seq data from diagnostic tissues of patients with (<i>n</i> = <i>19</i>) or without (<i>n</i> = <i>16</i>) sCNSi. CNS tropism of DLBCL cells was associated with increased expression of genes involved in PI3K-Akt-mTOR and ARF6 trafficking signaling and decreased expression of sphingosine-1-phosphate receptor signaling. Patient-derived transcriptomes exhibited enrichment of pathways that were functionally related to the gene signatures observed in the xenograft model. These findings suggest that CNS-preferential dissemination in DLBCL is associated with coordinated signaling involving PI3K/ARF6 activation and suppression of S1P-mediated pathways, providing molecular insights with potential implications for risk stratification and therapeutic targeting in sCNSi.</p>

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Transcriptomic profiling of an in vivo diffuse large B-cell lymphoma model reveals molecular programs underlying CNS dissemination

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • So-Jeong Kim,
  • Hyo-Kyung Pak,
  • Hyunji Kim,
  • Yongjun Lee,
  • Hwal-Seok Choi,
  • Jin-Woo Choi,
  • Do Eon Kim,
  • Jaewon Hyung,
  • Hyungwoo Cho,
  • Dok Hyun Yoon,
  • Jin Roh,
  • Chan-Sik Park

摘要

Secondary central nervous system involvement (sCNSi) is a fatal complication of diffuse large B-cell lymphoma (DLBCL), yet its molecular determinants remain poorly understood. To investigate the mechanisms underlying CNS-preferential dissemination, we established an in vivo DLBCL xenograft model using two representative cell lines, OCI-LY19 and Toledo, followed by transcriptomic profiling of lymphoma cells isolated from the brain, peripheral organs, and parental cultures. Transcriptomic analyses revealed gene signatures associated with CNS-preferential dissemination, which were further evaluated in RNA-seq data from diagnostic tissues of patients with (n = 19) or without (n = 16) sCNSi. CNS tropism of DLBCL cells was associated with increased expression of genes involved in PI3K-Akt-mTOR and ARF6 trafficking signaling and decreased expression of sphingosine-1-phosphate receptor signaling. Patient-derived transcriptomes exhibited enrichment of pathways that were functionally related to the gene signatures observed in the xenograft model. These findings suggest that CNS-preferential dissemination in DLBCL is associated with coordinated signaling involving PI3K/ARF6 activation and suppression of S1P-mediated pathways, providing molecular insights with potential implications for risk stratification and therapeutic targeting in sCNSi.