ArticleBlood2011
p53 activation of mesenchymal stromal cells partially abrogates microenvironment-mediated resistance to FLT3 inhibition in AML through HIF-1α-mediated down-regulation of CXCL12.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 103 citations in OpenAlex.
- Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms.Nature communications · 2019Trial
- AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.Molecular cancer · 2026Article
- AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.Research square · 2026Article
- Review
- Natural extract-derived compounds for the treatment of hematological diseases through modulation of the bone marrow microenvironment.Frontiers in chemistry · 2026Review
- Deciphering the molecular landscape of acute myeloid leukemia initiation and relapse: a systems biology approach.Medical oncology (Northwood, London, England) · 2025Review
- Targeting p53-p21 signaling to enhance mesenchymal stem cell regenerative potential.Regenerative therapy · 2025Review
- HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects.Cellular and molecular life sciences : CMLS · 2025Review
- Proteomic and metabolomic exploration in relapse acute myeloid leukemia bone marrow supernatant combined with genetic characteristics.BMC cancer · 2024Article
- CXCR4 as a therapeutic target in acute myeloid leukemia.Leukemia · 2024Review
- Multiparametric analysis of etoposide exposed mesenchymal stem cells and Fanconi anemia cells: implications in development of secondary myeloid malignancy.Clinical and experimental medicine · 2023Article
- The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways.Cell communication and signaling : CCS · 2023Review
- Mdm2/p53 levels in bone marrow mesenchymal stromal cells are essential for maintaining the hematopoietic niche in response to DNA damage.Cell death & disease · 2023Article
- Choosing the Right Cell Line for Acute Myeloid Leukemia (AML) Research.International journal of molecular sciences · 2023Review
- Mdm2/p53 levels in bone marrow mesenchymal stromal cells is essential for maintaining the hematopoietic niche in response to DNA damage.Research square · 2023Article
- A novel fatty acid metabolism-related signature identifies features of the tumor microenvironment and predicts clinical outcome in acute myeloid leukemia.Lipids in health and disease · 2022Article
- Acute Myeloid Leukemia Cells Educate Mesenchymal Stromal Cells toward an Adipogenic Differentiation Propensity with Leukemia Promotion Capabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- The mechanisms of mutual relationship between malignant hematologic cells and mesenchymal stem cells: Does it contradict the nursing role of mesenchymal stem cells?Cell communication and signaling : CCS · 2022Review
- Article
- Specific overexpression of SIRT1 in mesenchymal stem cells rescues hematopoiesis niche in BMI1 knockout mice through promoting CXCL12 expression.International journal of biological sciences · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Fms-like tyrosine kinase-3 (FLT3) inhibitors have been used to overcome the dismal prognosis of acute myeloid leukemia (AML) with FLT3 mutations. Clinical results with FLT3 inhibitor monotherapy have shown that bone marrow responses are commonly less pronounced than peripheral blood responses. We investigated the role of p53 in bone marrow stromal cells in stromal cell-mediated resistance to FLT3 inhibition in FLT3 mutant AML. While the FLT3 inhibitor FI-700 induced apoptosis in FLT3 mutant AML cells, apoptosis induction was diminished under stromal coculture conditions. Protection appeared to be mediated, in part, by CXCL12 (SDF-1)/CXCR4 signaling. The protective effect of stromal cells was significantly reduced by pre-exposure to the HDM2 inhibitor Nutlin-3a. p53 activation by Nutlin-3a was not cytotoxic to stromal cells, but reduced CXCL12 mRNA levels and secretion of CXCL12 partially through p53-mediated HIF-1α down-regulation. Results show that p53 activation in stroma cells blunts stroma cell-mediated resistance to FLT3 inhibition, in part through down-regulation of CXCL12. This is the first report of Nutlin effect on the bone marrow environment. We suggest that combinations of HDM2 antagonists and FLT3 inhibitors may be effective in clinical trials targeting mutant FLT3 leukemias.
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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.