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December 8, 2025BloodOpen Access

NAMPT in macrophages promotes multiple myeloma drug resistance through mitochondrial metabolic reprogramming and modulates immunosuppression via the SIRT1/STAT3/SPP1 axis.

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Authors

SYShunnan YaoXHXi HuangQSQi-Qi Shen

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Overview

Observational analysis revealed NAMPT modulates drug resistance and T cell dysfunction in macrophages, suggesting new therapeutic strategies for myeloma.

Key Points

  • Drug resistance in multiple myeloma was linked to macrophage interactions, particularly through NAMPT activity and mMΦ-induced T cell dysfunction.
  • NAD+ metabolism, influenced by NAMPT and SIRT1, was found to regulate immune responses in multiple myeloma environments.
  • Single-cell RNA sequencing identified macrophages in the tumor microenvironment as pivotal in mediating immune suppression during therapy.
  • Targeting NAMPT may enhance therapeutic efficacy against multiple myeloma by restoring T cell function and reducing drug resistance.

Cite This Study

Yao et al. (2025) studied this question.

synapsesocial.com/papers/69362f444fa91c937236d5e6https://doi.org/10.1182/blood-2025-5707
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Also Consider

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

  1. 1Targeting nicotinamide salvage pathway is a unique metabolic vulnerability of high-risk MDS stem cells2025
  2. 2Combinatorial targeting of metabolic vulnerabilities in t-cell leukemia through NAMPT inhibition2025
  3. 3NAD Metabolism Regulates Proliferation of Macrophages in Atherosclerosis2025 · 7 citations
  4. 4PSMD3 orchestrates metabolic reprogramming and immunogenic cell death in multiple myeloma2025
  5. 5Multi-omics reveals immune features in immune and non-immune cells, an IFN-γ/IFN-α-B2M positive feedback loop, and targeted metabolic therapy in multiple myeloma2025