ArticleThe Journal of clinical investigation2020
Pharmacogenomics of intracellular methotrexate polyglutamates in patients' leukemia cells in vivo.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Pooled it
- Trial
- Phenotype-Specific Pharmacogenetic Patterns of Methotrexate Neurotoxicity in Pediatric Acute Lymphoblastic Leukemia.Journal of clinical medicine · 2026Article
- Pharmacogenomics in Pediatric Oncology Research and Treatment.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2024Article
- Article
- Integrative transcriptome analysis identifies MYBL2 as a poor prognosis marker for osteosarcoma and a pan-cancer marker of immune infiltration.Genes & diseases · 2024Article
- Anticancer therapy-induced adverse drug reactions in children and preventive and control measures.Frontiers in pharmacology · 2024Review
- Prognostic and Pharmacotypic Heterogeneity of Hyperdiploidy in Childhood ALL.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response.Pharmaceuticals (Basel, Switzerland) · 2022Review
- CircFBXW7 inhibits the tumorigenesis of T-cell acute lymphoblastic leukemia through modulating miR-494-3p/SOX1 axis.Cell death discovery · 2022Article
- Glutathione levels are associated with methotrexate resistance in acute lymphoblastic leukemia cell lines.Frontiers in oncology · 2022Article
- Inokosterone Is A Potential Drug Target of Estrogen Receptor 1 in Rheumatoid Arthritis Patients: Analysis from Active Ingredient of Cyathula Officinalis.Chinese journal of integrative medicine · 2021Article
- Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia.Journal of clinical medicine · 2021Review
- New insights into methotrexate accumulation in leukemia cellsMolecular & cellular oncology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUNDInterpatient differences in the accumulation of methotrexate's active polyglutamylated metabolites (MTXPGs) in leukemia cells influence its antileukemic effects.METHODSTo identify genomic and epigenomic and patient variables determining the intracellular accumulation of MTXPGs, we measured intracellular MTXPG levels in acute lymphoblastic leukemia (ALL) cells from 388 newly diagnosed patients after in vivo high-dose methotrexate (HDMTX) (1 g/m2) treatment, defined ALL subtypes, and assessed genomic and epigenomic variants influencing folate pathway genes (mRNA, miRNA, copy number alterations [CNAs], SNPs, single nucleotide variants [SNVs], CpG methylation).RESULTSWe documented greater than 100-fold differences in MTXPG levels, which influenced its antileukemic effects (P = 4 × 10-5). Three ALL subtypes had lower MTXPG levels (T cell ALL [T-ALL] and B cell ALL [B-ALL] with the TCF3-PBX1 or ETV6-RUNX1 fusions), and 2 subtypes had higher MTXPG levels (hyperdiploid and BCR-ABL like). The folate pathway genes SLC19A1, ABCC1, ABCC4, FPGS, and MTHFD1 significantly influenced intracellular MTXPG levels (P = 2.9 × 10-3 to 3.7 × 10-8). A multivariable model including the ALL subtype (P = 1.1 × 10-14), the SLC19A1/(ABCC1 + ABCC4) transporter ratio (P = 3.6 × 10-4), the MTX infusion time (P = 1.5 × 10-3), FPGS mRNA expression (P = 2.1 × 10-3), and MTX systemic clearance (P = 4.4 × 10-2) explained 42% of the variation in MTXPG accumulation (P = 1.1 × 10-38). Model simulations indicated that a longer infusion time (24 h vs. 4 h) was superior in achieving higher intracellular MTXPG levels across all subtypes if ALL.CONCLUSIONSThese findings provide insights into mechanisms underlying interpatient differences in intracellular accumulation of MTXPG in leukemia cells and its antileukemic effectsFUNDINGTHE National Cancer Institute (NCI) and the Institute of General Medical Sciences of the NIH, the Basque Government Programa Posdoctoral de Perfeccionamiento de Personal Investigador doctor, and the American Lebanese Syrian Associated Charities (ALSAC).
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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.