ArticleJournal of cellular and molecular medicine2019
Regulation of drug metabolizing enzymes in the leukaemic bone marrow microenvironment.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Arsenic trioxide for reprogramming the bone marrow microenvironment to eliminate acute myeloid leukemia blasts.HemaSphere · 2025Article
- The Dual PIM/FLT3 Inhibitor MEN1703 Combines Synergistically With Gilteritinib in FLT3-ITD-Mutant Acute Myeloid Leukaemia.Journal of cellular and molecular medicine · 2024Article
- Modelling post-chemotherapy stem cell dynamics in the bone marrow niche of AML patients.Scientific reports · 2024Article
- Review
- Random walk with restart on multilayer networks: from node prioritisation to supervised link prediction and beyond.BMC bioinformatics · 2024Article
- Article
- Article
- Bone marrow stromal cells reduce low-dose cytarabine-induced differentiation of acute myeloid leukemia.Frontiers in pharmacology · 2023Article
- Boosting the oral bioavailability of anticancer drugs through intentional drug-drug interactions.Basic & clinical pharmacology & toxicology · 2022Review
- Expression Profile Screening and Bioinformatics Analysis of circRNA, LncRNA, and mRNA in Acute Myeloid Leukemia Drug-Resistant CellsTurkish journal of haematology : official journal of Turkish Society of Haematology · 2020Article
- Targeting the Microenvironment in MDS: The Final Frontier.Frontiers in pharmacology · 2020Review
- Regulation of drug metabolizing enzymes in the leukaemic bone marrow microenvironment.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The bone marrow (BM) microenvironment contributes to drug resistance in acute myeloid leukaemia (AML) and multiple myeloma (MM). We have shown that the critical drug metabolizing enzymes cytochrome P450 (CYP) 3A4 and cytidine deaminase (CDA) are highly expressed by BM stroma, and play an important role in this resistance to chemotherapy. However, what factors influence the chemoprotective capacity of the BM microenvironment, specifically related to CYP3A4 and CDA expression, are unknown. In this study, we found that the presence of AML cells decreases BM stromal expression of CYP3A4 and CDA, and this effect appears to be at least partially the result of cytokines secreted by AML cells. We also observed that stromal CYP3A4 expression is up-regulated by drugs commonly used in AML induction therapy, cytarabine, etoposide and daunorubicin, resulting in cross-resistance. Cytarabine also up-regulated CDA expression. The up-regulation of CYP3A4 associated with disease control was reversed by clarithromycin, a potent inhibitor of CYP3A4. Our data suggest that minimal residual disease states are characterized by high levels of stromal drug metabolizing enzymes and thus, strong microenvironment-mediated drug resistance. These results further suggest a potential role for clinically targeting drug metabolizing enzymes in the microenvironment.
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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.