ArticleCancer discovery2022
Subversion of Serotonin Receptor Signaling in Osteoblasts by Kynurenine Drives Acute Myeloid Leukemia.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 31 citations in OpenAlex.
- The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia.Biomedicines · 2026Review
- Branching architecture of tryptophan metabolism determines therapeutic vulnerability in acute myeloid leukemia.Cell death & disease · 2026Article
- Intrinsic and niche-dependent metabolic regulation of haematopoietic stem cells and implications for leukaemogenesis.Nature cell biology · 2026Review
- Regulatory role of mTORC1 signaling in osteoblasts in acute myeloid leukemia progression and steady-state hematopoiesis.iScience · 2026Article
- Mitochondrial transfer-mediated metabolic reprogramming and drug resistance in bone metastasis: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Article
- Amino acid metabolic reprogramming drives pathogenesis and therapy in hematologic malignancies.Discover oncology · 2025Review
- Multifaceted role of the vitamin B6 pathway in cancer: metabolism, immune interaction, and temporal and spatial regulation.Genes & development · 2025Review
- Engineered red blood cell extracellular vesicles for delivery of Dox and siIDO1 enhance targeted chemo-immunotherapy of acute myeloid leukemia.Journal for immunotherapy of cancer · 2025Article
- From Chemotherapy to Targeted Therapy: Unraveling Resistance in Acute Myeloid Leukemia Through Genetic and Non-Genetic Insights.International journal of molecular sciences · 2025Review
- SAA1 Protein: A Potential Biomarker for Acute Myeloid Leukemia.Biomedicines · 2025Article
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Tryptophan 2,3-dioxygenase-positive matrix fibroblasts fuel breast cancer lung metastasis via kynurenine-mediated ferroptosis resistance of metastatic cells and T cell dysfunction.Cancer communications (London, England) · 2024Article
- Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment.Biomarker research · 2024Review
- Remodeling of the bone marrow microenvironment during acute myeloid leukemia progression.Annals of translational medicine · 2024Review
- Senescence in the bone marrow microenvironment: A driver in development of therapy-related myeloid neoplasms.Journal of bone oncology · 2024Article
- Metabolic regulation of skeletal cell fate and function.Nature reviews. Endocrinology · 2024Review
- Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression.International journal of molecular sciences · 2024Review
- Article
- Bone Marrow Adipose Tissue: Regulation of Osteoblastic Niche, Hematopoiesis and Hematological Malignancies.Stem cell reviews and reports · 2023Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
Remodeling of the microenvironment by tumor cells can activate pathways that favor cancer growth. Molecular delineation and targeting of such malignant-cell nonautonomous pathways may help overcome resistance to targeted therapies. Herein we leverage genetic mouse models, patient-derived xenografts, and patient samples to show that acute myeloid leukemia (AML) exploits peripheral serotonin signaling to remodel the endosteal niche to its advantage. AML progression requires the presence of serotonin receptor 1B (HTR1B) in osteoblasts and is driven by AML-secreted kynurenine, which acts as an oncometabolite and HTR1B ligand. AML cells utilize kynurenine to induce a proinflammatory state in osteoblasts that, through the acute-phase protein serum amyloid A (SAA), acts in a positive feedback loop on leukemia cells by increasing expression of IDO1-the rate-limiting enzyme for kynurenine synthesis-thereby enabling AML progression. This leukemia-osteoblast cross-talk, conferred by the kynurenine-HTR1B-SAA-IDO1 axis, could be exploited as a niche-focused therapeutic approach against AML, opening new avenues for cancer treatment. SIGNIFICANCE: AML remains recalcitrant to treatments due to the emergence of resistant clones. We show a leukemia-cell nonautonomous progression mechanism that involves activation of a kynurenine-HTR1B-SAA-IDO1 axis between AML cells and osteoblasts. Targeting the niche by interrupting this axis can be pharmacologically harnessed to hamper AML progression and overcome therapy resistance. This article is highlighted in the In This Issue feature, p. 873.
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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.