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December 8, 2025Blood

Multi-omics analysis identifies neutrophil degranulation as a PSMD3-regulated pathway in FLT3-mutated AML

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Authors

SDSaeedeh DarvishiSSSharon SibyMBM.M. Black

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Overview

This research identifies neutrophil degranulation as a regulated pathway in FLT3-mutated AML, suggesting a role for drug resistance mechanisms.

Key Points

  • Explore the role of PSMD3 in drug resistance and pathways involved in FLT3-mutated AML.
  • Generated a resistant MOLM-14 AML cell line via Midostaurin exposure.
  • Validated resistance using colony formation and cell viability assays.
  • Conducted single-cell RNA sequencing to analyze sensitive and resistant cells.
  • Analyzed metabolic changes via lipidomics and metabolomics profiling.
  • Neutrophil degranulation identified as a top dysregulated pathway in PSMD3-depleted MOLM-14 cells.
  • PSMD3 reduction decreased colony formation in both TKI-sensitive and -resistant conditions.
  • Significant metabolic changes observed post-PSMD3 knockdown, with broad reprogramming of lipid and metabolic pathways.

Cite This Study

Darvishi et al. (2025) studied this question.

synapsesocial.com/papers/69362f7f4fa91c937236e511https://doi.org/10.1182/blood-2025-6757
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Also Consider

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

  1. 1PSMD3 orchestrates metabolic reprogramming and immunogenic cell death in multiple myeloma2025
  2. 2Targeting METTL3 disrupts oncogenic transcriptional programs and activates immune and apoptotic pathways in Acute Myeloid Leukemia2025
  3. 3Targeting CCL3+mono like LSC overcomes chemotherapy resistance in NPM1 mutant AML2025
  4. 4Proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), play an oncogenic role in chronic myeloid leukemia by stabilizing nuclear factor-kappa B2021 · 42 citations
  5. 5Selective targeting of RSK signaling with PMD-026 suppresses FLT3-activated acute myeloid leukemia while sparing normal hematopoiesis2026 · 1 citations