ArticleOncotarget2015
Human bone marrow niche chemoprotection mediated by cytochrome P450 enzymes.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Pharmacological boosting of azacitidine/venetoclax in acute myeloid leukemia.Blood neoplasia · 2026Trial
- Differentiation therapy in poor risk myeloid malignancies: Results of companion phase II studies.Leukemia research · 2016Trial
- Sterol Metabolism in Ovariectomized Rats: Potential Roles of Campesterol and 4β-Hydroxycholesterol in Osteoporosis.Lipids · 2026Article
- Arsenic trioxide for reprogramming the bone marrow microenvironment to eliminate acute myeloid leukemia blasts.HemaSphere · 2025Article
- Review
- Overcoming the sorafenib resistance mechanism in FLT3-mutated acute myeloid leukemia: molecular basis and new targets.Frontiers in oncology · 2025Review
- Review
- Skin mesenchymal niches maintain and protect AML-initiating stem cells.The Journal of experimental medicine · 2023Article
- Genotoxicity of cytokines at chemotherapy-induced 'storm' concentrations in a model of the human bone marrow.Mutagenesis · 2023Article
- Article
- Article
- Microphysiological Drug-Testing Platform for Identifying Responses to Prodrug Treatment in Primary Leukemia.Advanced healthcare materials · 2023Article
- Overcoming Resistance: FLT3 Inhibitors Past, Present, Future and the Challenge of Cure.Cancers · 2022Review
- A novel in vitro 3D model of the human bone marrow to bridge the gap between in vitro and in vivo genotoxicity testing.Mutagenesis · 2022Article
- A review of FLT3 inhibitors in acute myeloid leukemia.Blood reviews · 2022Review
- The hedgehog pathway in hematopoiesis and hematological malignancy.Frontiers in oncology · 2022Review
- The immunological role of mesenchymal stromal cells in patients with myelodysplastic syndrome.Frontiers in immunology · 2022Review
- Tumour Microenvironment Stress Promotes the Development of Drug Resistance.Antioxidants (Basel, Switzerland) · 2021Review
- Establishment of Prognosis Model in Acute Myeloid Leukemia Based on Hypoxia Microenvironment, and Exploration of Hypoxia-Related Mechanisms.Frontiers in genetics · 2021Article
- Novel Approaches to Target Mutant FLT3 Leukaemia.Cancers · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Substantial evidence now demonstrates that interactions between the tumor microenvironment and malignant cells are a critical component of clinical drug resistance. However, the mechanisms responsible for microenvironment-mediated chemoprotection remain unclear. We showed that bone marrow (BM) stromal cytochrome P450 (CYP)26 enzymes protect normal hematopoietic stem cells (HSCs) from the pro-differentiation effects of retinoic acid. Here, we investigated if stromal expression of CYPs is a general mechanism of chemoprotection. We found that similar to human hepatocytes, human BM-derived stromal cells expressed a variety of drug-metabolizing enzymes. CYP3A4, the liver's major drug-metabolizing enzyme, was at least partially responsible for BM stroma's ability to protect multiple myeloma (MM) and leukemia cells from bortezomib and etoposide, respectively, both in vitro and in vivo. Moreover, clarithromycin overcame stromal-mediated MM resistance to dexamethasone, suggesting that CYP3A4 inhibition plays a role in its ability to augment the activity of lenalidomide and dexamethasone as part of the BiRd regimen. We uncovered a novel mechanism of microenvironment-mediated drug resistance, whereby the BM niche creates a sanctuary site from drugs. Targeting these sanctuaries holds promise for eliminating minimal residual tumor and improving cancer outcomes.
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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.