Publications by authors named "S W Paugh"
Article Synopsis
- Vincristine is a medicine used to treat certain types of cancer in both kids and adults, but it can cause nerve damage called peripheral neuropathy, which can last a long time.
- Researchers found that a low level of a protein called NHP2L1 makes leukemia cells more sensitive to Vincristine, meaning it works better against cancer.
- Giving Vincristine with NHP2L1 blockers helps fight leukemia more effectively while reducing nerve damage in mice, which could help improve the treatment for cancer patients without hurting their quality of life.
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).
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- Research identified 463 genomic features linked to glucocorticoid resistance in acute lymphoblastic leukemia using a comprehensive analysis of mRNA, miRNA, and other genetic factors.
- A total of 118 overlapping genes were found, including 30 out of 38 known glucocorticoid-resistance genes, along with 14 new genes connected to resistance.
- The study highlighted CELSR2 as a significant player in glucocorticoid resistance, leading to the discovery of a potential new drug combination that could combat resistance in leukemia treatments.
Gene signatures have been associated with outcome in pediatric acute lymphoblastic leukemia (ALL) and other malignancies. However, determining the molecular drivers of these expression changes remains challenging. In ALL blasts, the p53 tumor suppressor is the primary regulator of the apoptotic response to genotoxic chemotherapy, which is predictive of outcome.
View Article and Find Full Text PDFThe causes of individual relapses in children with acute lymphoblastic leukemia (ALL) remain incompletely understood. We evaluated the contribution of germline genetic factors to relapse in 2225 children treated on Children's Oncology Group trial AALL0232. We identified 302 germline single-nucleotide polymorphisms (SNPs) associated with relapse after adjusting for treatment and ancestry and 715 additional SNPs associated with relapse in an ancestry-specific manner.
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