Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
December 8, 2025Blood

LSD1 inhibition enhances venetoclax efficacy in Acute Myeloid Leukemia via metabolic rewiring

View Full Paper
Ask AI
Bookmark
Share

Authors

EHEmily HartungSPSara PishyarPPPradhariny Prabagaran

Discussion

Loading...

Member takes

Overview

Inhibition of LSD1 improves apoptosis in leukemic stem cells, implying enhanced metabolic reprogramming and effectiveness of venetoclax.

Key Points

  • To investigate the effect of LSD1 inhibition on the efficacy of venetoclax in treating acute myeloid leukemia (AML).
  • Assessed cytotoxic effects of venetoclax and bomedemstat in various AML cell lines and primary samples.
  • Evaluated in vivo efficacy in patient-derived xenograft models using AML samples.
  • Analyzed metabolic changes using Seahorse® and NMR spectrometry.
  • Conducted RNA sequencing to examine gene expression changes related to metabolism.
  • Co-treatment of bomedemstat and venetoclax showed synergistic cytotoxicity in 19 out of 26 primary AML samples.
  • Bomedemstat significantly enhanced apoptosis in MOLM-13 cells treated with venetoclax.
  • Combination treatment resulted in reduced glycolysis and increased oxidative phosphorylation, indicative of metabolic rewiring.
  • Bomedemstat activated AMPK, suppressing lipid biosynthesis and shifting energy metabolism.

Cite This Study

Hartung et al. (2025) studied this question.

synapsesocial.com/papers/69362f444fa91c937236d5e0https://doi.org/10.1182/blood-2025-3293
View Full Paper
Ask AI
Bookmark
Share