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December 8, 2025BloodOpen Access

Evidence for pre-existing myeloma cells with a gene expression pattern associated with resistance to BCMA CAR T cells.

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Authors

LHLondon HarperHLHolly LeePNPaola Neri

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Overview

Spatiotemporal genomic analysis reveals pre-existing myeloma cells resistant to BCMA CAR T therapy, suggesting a need for enhanced patient screening.

Key Points

  • Pre-existing myeloma cells exhibit a gene expression pattern linked to resistance against BCMA CAR T therapy, indicating therapeutic challenges.
  • RNA sequencing highlighted crucial genes involved in cytokine signaling, unfolded protein response, and WNT signaling in resistant cells.
  • KMS cell lines served as the model for analyzing engagement duration and resistance mechanisms, using live imaging and staining methods.
  • Identifying resistant myeloma cells through single cell analysis could inform treatment decisions and improve clinical outcomes.

Cite This Study

Harper et al. (2025) studied this question.

synapsesocial.com/papers/69362f3a4fa91c937236d437https://doi.org/10.1182/blood-2025-1031
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Also Consider

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

  1. 1The dynamic landscape of immune environment for MM patients receiving T cell redirectiing therapies2025
  2. 2Impact of prior BCMA-targeted therapy on CAR-T expansion and host T-cell phenotypes in patients with Relapsed/Refractory multiple myeloma receiving BCMA CAR-T therapy2025
  3. 3Identification of persister cells and evolution of tumor clones during immunotherapy and at minimal residual disease timepoints decoded by single-cell whole-genome sequencing in multiple myeloma2025
  4. 4Functional fitness of CAR-T cells in the bone marrow following anti-BCMA durcabtagene autoleucel (PHE885) therapy correlate with prolonged PFS in RRMM2025
  5. 5Kinetics of circulating multiple myeloma cells (CMMCs) in patients undergoing standard-of-care anti-BCMA chimeric antigen receptor T cell therapy for Relapsed/Refractory multiple myeloma2025 · 1 citations