ArticleLeukemia2010
Histone deacetylase inhibitors induce FPGS mRNA expression and intracellular accumulation of long-chain methotrexate polyglutamates in childhood acute lymphoblastic leukemia: implications for combination therapy.
Article in Leukemia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
26 citing papers in PubMed, 52 citations in OpenAlex.
- Molecular dissection of valproic acid effects in acute myeloid leukemia identifies predictive networks.Epigenetics · 2016Trial
- Histone deacetylase inhibitors: targeting epigenetic regulation in the treatment of acute leukemia.Therapeutic advances in hematology · 2024Review
- Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: a systematic review.Frontiers in oncology · 2024Review
- Methotrexate Polyglutamates Analysis by Chromatography Methods in Biological Matrices: A Review.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2021Review
- The advances of methotrexate resistance in rheumatoid arthritis.Inflammopharmacology · 2020Review
- HDACi mediate UNG2 depletion, dysregulated genomic uracil and altered expression of oncoproteins and tumor suppressors in B- and T-cell lines.Journal of translational medicine · 2020Article
- Enzymes involved in folate metabolism and its implication for cancer treatment.Nutrition research and practice · 2020Review
- β-catenin promotes MTX resistance of leukemia cells by down-regulating FPGS expression via NF-κB.Cancer cell international · 2020Article
- Glutamic Acid Increased Methotrexate Polyglutamation and Cytotoxicity in a CCRF-SB Acute Lymphoblastic Leukemia Cell Line.Medicina (Kaunas, Lithuania) · 2019Article
- Clinicopathological features and prediction values of HDAC1, HDAC2, HDAC3, and HDAC11 in classical Hodgkin lymphoma.Anti-cancer drugs · 2018Article
- Clinical significance of polyglutamylation in primary central nervous system lymphoma.Acta neuropathologica communications · 2018Article
- Effect of the Polymorphism of Folylpolyglutamate Synthetase on Treatment of High-Dose Methotrexate in Pediatric Patients with Acute Lymphocytic Leukemia.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Methotrexate resistance in relation to treatment outcome in childhood acute lymphoblastic leukemia.Journal of hematology & oncology · 2015Article
- Selective Inhibition of HDAC1 and HDAC2 as a Potential Therapeutic Option for B-ALL.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Novel agents for the treatment of childhood acute leukemia.Therapeutic advances in hematology · 2015Review
- Histone acetylation: novel target for the treatment of acute lymphoblastic leukemia.Clinical epigenetics · 2015Review
- Article
- Pediatric relapsed or refractory leukemia: new pharmacotherapeutic developments and future directions.Drugs · 2013Review
- A phase I trial of vorinostat and bortezomib in children with refractory or recurrent solid tumors: a Children's Oncology Group phase I consortium study (ADVL0916).Pediatric blood & cancer · 2013Article
- Influence of Histone Deacetylase Inhibitors and DNA-Methyltransferase Inhibitors on the NK Cell-Mediated Lysis of Pediatric B-Lineage Leukemia.Frontiers in oncology · 2013Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
Children with acute lymphoblastic leukemia (ALL) diagnosed with resistant phenotypes, and those who relapse, have a dismal prognosis for cure. The antifolate methotrexate (MTX), a universal component of ALL therapies, is metabolized by folylpoly-gamma-glutamate synthetase (FPGS) into long-chain polyglutamates (MTX-PG(3-7)), resulting in enhanced cytotoxicity from prolonged inhibition of dihydrofolate reductase (DHFR) and thymidylate synthetase (TS). Using DNaseI assays, we identified a hypersensitive site upstream from exon-1, suggesting chromatin remodeling could alter FPGS expression. We demonstrated that histone deacetylase-1 (HDAC1) is recruited by NFY and Sp1 transcription factors to the FPGS promoter in ALL cell lines. We examined the effect of histone deacetylase inhibitors (HDACIs) sodium butyrate and suberoylanilide hydroxamic acid (SAHA) on the expression of FPGS and other folate-related genes. HDACIs increased FPGS mRNA expression by 2- to 5-fold, whereas DHFR and TS mRNA expression was decreased. Combination treatment with MTX plus SAHA significantly increased cytotoxicity and apoptosis in B- and T-ALL cell lines as compared with each drug alone (CI<or=0.8). SAHA increased the intracellular accumulation of long-chain MTX-PG(3-7). Therefore, HDACI-induced FPGS expression increases the accumulation of MTX-PG(3-7) and cytotoxicity in ALL cell lines, which is potentiated by DHFR and TS downregulation. The synergism exhibited by the combination of MTX and SAHA warrants clinical testing in ALL patients.
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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.