ArticleBlood2024
PI3Kγ maintains the self-renewal of acute myeloid leukemia stem cells by regulating the pentose phosphate pathway.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 25 citations in OpenAlex.
- Defining and managing high-risk acute myeloid leukemia (AML) in 2026.Annals of hematology · 2026Review
- Serglycin-ROS axis mediates synergistic lethality of PI3Kγ inhibition and Azacitidine in TP53-mutated AML.BMC cancer · 2026Article
- Transcriptomic analysis of differential expression and correlation of coding and non-coding RNAs in urine from patients with idiopathic membranous nephropathy.Biology direct · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- SEMA4A promotes acute myeloid leukemia progression through inhibiting apoptosis.Genes & genomics · 2026Article
- Exploiting tumor lineage features for precision cancer therapy.Trends in cancer · 2026Review
- FBXO3-mediated DUSP9 ubiquitination promotes leukemia stem cell maintenance and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Cell reports. Medicine · 2026Article
- cellMCD Effectively Discovers Drug Resistance and Sensitivity Genes for Acute Myeloid Leukemia.Genes · 2026Article
- Critical role of niche S100A8 for acute myeloid leukemia progression and hematopoiesis regeneration.Blood advances · 2025Article
- LncRNA NEAT1 restrains the malignant biological characteristics of acute myeloid leukemia via regulating CTCF/CXCR2 axis.Clinical and experimental medicine · 2025Article
- Predicting immunotherapeutic response and therapeutic targets by stemness classification of acute myeloid leukemia by stemness score.Discover oncology · 2025Article
- Review
- TKT regulates the pentose phosphate pathway via RBKS to promote epithelial-mesenchymal transition during AML progression.Journal of bioenergetics and biomembranes · 2025Article
- Review
- Targeting PI3Kγ in cancer.Trends in cancer · 2025Review
- ARF6 Promotes AML Progression via Activation of PI3K/AKT/mTOR Signaling.Cancer medicine · 2025Article
- From Chemotherapy to Targeted Therapy: Unraveling Resistance in Acute Myeloid Leukemia Through Genetic and Non-Genetic Insights.International journal of molecular sciences · 2025Review
- Identification of glucuronic acid as a biomarker of poor prognosis in acute myeloid leukemia based on plasma metabolomics.Clinical and experimental medicine · 2025Article
- STING exerts antiviral innate immune response by activating pentose phosphate pathway.Cell communication and signaling : CCS · 2024Article
- Noncanonical PI3Kγ signaling addiction is a therapeutic target in a subset of leukemias.Innovation (Cambridge (Mass.)) · 2024Review
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
abstractAcute myeloid leukemia (AML) is an aggressive hematological malignancy originating from transformed hematopoietic stem or progenitor cells. AML prognosis remains poor owing to resistance and relapse driven by leukemia stem cells (LSCs). Targeting molecules essential for LSC function is a promising therapeutic approach. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is often dysregulated in AML. We found that although PI3Kγ is highly enriched in LSCs and critical for self-renewal, it was dispensable for normal hematopoietic stem cells. Mechanistically, PI3Kγ-AKT signaling promotes nuclear factor erythroid 2-related factor 2 (NRF2) nuclear accumulation, which induces 6-phosphogluconate dehydrogenase (PGD) and the pentose phosphate pathway, thereby maintaining LSC stemness. Importantly, genetic or pharmacological inhibition of PI3Kγ impaired expansion and stemness of murine and human AML cells in vitro and in vivo. Together, our findings reveal a key role for PI3Kγ in selectively maintaining LSC function by regulating AKT-NRF2-PGD metabolic pathway. Targeting the PI3Kγ pathway may, therefore, eliminate LSCs without damaging normal hematopoiesis, providing a promising therapeutic strategy for AML.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.