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December 8, 2025BloodOpen Access

MYC-dependent permissiveness of PI3K hyperactivation renders metabolic vulnerability in R/R b-ALL

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Authors

JJJian‐Ping JinHHHe HuangMMMarkus Müschen

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Overview

Findings reveal glutaminolysis and redox imbalance as critical factors in relapsed B-ALL, suggesting new treatment strategies.

Key Points

  • This research aims to explore how MYC-dependent PI3K hyperactivation affects metabolism in relapsed B-ALL.
  • Genetic augmentation of MYC expression in B-ALL cells was performed.
  • Combination of Duvelisib with CAR-T therapy was tested in xenograft models.
  • Metabolomic profiling and NADH/NAD+ ratio were analyzed in PI3KhiMYCamp B-ALL cells.
  • Utilized transmission electron microscopy to assess mitochondrial structure changes.
  • MYC expression increases PI3K hyperactivation, leading to aggressive relapsed B-ALL.
  • Combination of Duvelisib and CAR-T therapy significantly extends survival in mouse models.
  • Elevated NADH levels were identified as a metabolic vulnerability in B-ALL cells.
  • Inhibition of Complex I and Pegaspargase effectively reduced PI3KhiMYCamp B-ALL cell proliferation.
  • Metabolomic profiling showed altered amino acid levels in PI3KhiMYCamp B-ALL cells.

Cite This Study

Jin et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dcc3https://doi.org/10.1182/blood-2025-1475
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Also Consider

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

  1. 1Targeted hyperactivation of oncogenic STAT5-signaling in acute lymphoblastic leukemia2025
  2. 2A metabolic synthetic lethality of PI3K-driven cancer2024
  3. 3Abstract 4758: MYC-BCL6 state transition drives metabolomic cycling and leukemia-initiating capacity in B-ALL2026
  4. 4Synergistic MDM2-STAT3 Inhibition Demonstrates Strong Anti-Leukemic Efficacy in Acute Lymphoblastic Leukemia2025 · 1 citations
  5. 5Abstract P30: Therapeutic activation of pre-B-cell receptor signaling in high-risk pediatric ALL: exploiting TCF3 and MYC-linked vulnerabilities2024