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December 8, 2025BloodOpen Access

CDK7 enables adaptive gene transcription required by stromal cells to support distinct T-cell lymphoma phenotypes and represents a novel microenvironment-directed therapeutic target

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Authors

GIGiorgio InghiramiNZNahuel Zamponi

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Overview

Findings show that CDK7 regulates transcription in stromal cells and enhances lymphoma cell survival, suggesting novel treatment avenues.

Key Points

  • This research investigates the role of CDK7 in stromal cells and its impact on T-cell lymphoma phenotypes.
  • Characterized lymphoma microenvironment using transcriptional signature deconvolution and imaging.
  • Established patient-derived tumor xenografts to study CAF and PTCL interactions.
  • Analyzed gene and protein expression changes following CDK7 inhibition using selective inhibitor YKL-5-124.
  • Conducted viability screenings with clinical-phase drug library in co-cultures of IN-PTCL and IN-CAF.
  • CDK7 inhibition altered gene expression in CAFs, impacting collagens and cytokines.
  • Matched co-cultures increased lymphoma cell proliferation compared to unmatched ones.
  • Identified 14 compounds with synergistic anti-lymphoma effects in co-cultures, including novel inhibitors.
  • CDK7 is required for maintaining pro-tumoral interactions in the lymphoma microenvironment.

Cite This Study

Inghirami et al. (2025) studied this question.

synapsesocial.com/papers/69362f5d4fa91c937236dc87https://doi.org/10.1182/blood-2025-554
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract 5720: Targeting CDK9 in cutaneous T-cell lymphoma using patient-derived xenograft models2024
  2. 2Abstract PR05: Single-cell transcriptomics reveals shared and subtype-specific vulnerabilities of the tumor-microenvironment ecosystems in peripheral T-cell lymphomas2024
  3. 3Single-nucleus dissection of peripheral T-cell lymphomas reveals distinct microenvironmental ecosystems and therapeutic vulnerabilities2025
  4. 4Abstract A056: Microenvironmental ecosystems in peripheral T-cell lymphomas reveal therapeutic vulnerabilities2026
  5. 5Targets of BTK and IRAK4 pathways in cns lymphoma: Identification of CXCL10 as a prognostic biomarker in CSF and its receptor, CXCR3, as a mediator of pro-survival signaling2025