ArticleThe Journal of clinical investigation2021
Bone marrow niche ATP levels determine leukemia-initiating cell activity via P2X7 in leukemic models.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Bone marrow stromal cells promote chemoresistance in acute myeloid leukaemia through P2RX7-mediated antioxidant defence.Experimental & molecular medicine · 2026Article
- Single-cell architecture of purinergic signaling in human cord blood hematopoietic stem and progenitor cells.Leukemia · 2026Article
- The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia.Biomedicines · 2026Review
- P2X7 receptor: An emerging therapeutic target in acute myeloid leukemia (Review).International journal of oncology · 2026Review
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Nonionotropic action of an acid-sensing ion channel inhibits leukemogenesis in the acidic bone marrow niche.The Journal of clinical investigation · 2025Article
- The P2X7 receptor in leukemia: pathological mechanisms and therapeutic potential.Purinergic signalling · 2025Review
- Protein post-translational modifications in serine synthetic pathway: functions and molecular mechanisms.Cell communication and signaling : CCS · 2025Review
- mNature communications · 2025Article
- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
- Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.International journal of molecular sciences · 2024Review
- NAT10-mediated mRNA NNature cell biology · 2024Article
- Remodeling of the bone marrow microenvironment during acute myeloid leukemia progression.Annals of translational medicine · 2024Review
- Metabolic regulation of skeletal cell fate and function.Nature reviews. Endocrinology · 2024Review
- Potential role of the P2X7 receptor in the proliferation of human diffused large B-cell lymphoma.Purinergic signalling · 2024Article
- Post-Transplant Cyclophosphamide Combined with Brilliant Blue G Reduces Graft-versus-Host Disease without Compromising Graft-versus-Leukaemia Immunity in Humanised Mice.International journal of molecular sciences · 2024Article
- The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk.International journal of molecular sciences · 2023Review
- TET2-mediated mRNA demethylation regulates leukemia stem cell homing and self-renewal.Cell stem cell · 2023Article
- ARHGAP4 promotes leukemogenesis in acute myeloid leukemia by inhibiting DRAM1 signaling.Oncogene · 2023Article
- Immunotherapy in leukaemia.Acta biochimica et biophysica Sinica · 2023Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
How particular bone marrow niche factors contribute to the leukemogenic activities of leukemia-initiating cells (LICs) remains largely unknown. Here, we showed that ATP levels were markedly increased in the bone marrow niches of mice with acute myeloid leukemia (AML), and LICs preferentially localized to the endosteal niche with relatively high ATP levels, as indicated by a sensitive ATP indicator. ATP could efficiently induce the influx of ions into LICs in an MLL-AF9-induced murine AML model via the ligand-gated ion channel P2X7. P2x7 deletion led to notably impaired homing and self-renewal capacities of LICs and contributed to an approximately 5-fold decrease in the number of functional LICs but had no effect on normal hematopoiesis. ATP/P2X7 signaling enhanced the calcium flux-mediated phosphorylation of CREB, which further transactivated phosphoglycerate dehydrogenase (Phgdh) expression to maintain serine metabolism and LIC fates. P2X7 knockdown resulted in a markedly extended survival of recipients transplanted with either human AML cell lines or primary leukemia cells. Blockade of ATP/P2X7 signaling could efficiently inhibit leukemogenesis. Here, we provide a perspective for understanding how ATP/P2X7 signaling sustains LIC activities, which may benefit the development of specific strategies for targeting LICs or other types of cancer stem cells.
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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.