ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2024
Impact of Age on Pharmacogenomics and Treatment Outcomes of B-Cell Acute Lymphoblastic Leukemia.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Developmental timing distinguishes pediatric and adult cancers through retention and rewiring mechanisms.Nature communications · 2026Review
- Article
- A review of treatment strategies for elderly patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia.Translational oncology · 2026Review
- Intra-subtype heterogeneity shapes treatment response inHemaSphere · 2026Article
- Review
- Age-Driven Genetic and Epigenetic Heterogeneity in B-ALL.International journal of molecular sciences · 2025Review
- CSF2RA promotes gastric cancer progression through activation of the JAK2/STAT3 signaling pathway.Journal of molecular histology · 2025Article
- Article
- The role of IKZF1 rs4132601 and Δ4-7 somatic deletion in acute lymphoblastic leukemia: a bioinformatics and case-control study.Molecular biology reports · 2025Article
- Review
- P2RX1 Influences the Prognosis of Ph+/Ph-Like ALL through Energy and Calcium Metabolism.Oncology research · 2025Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
purposeAcute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear.
methodsStudying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. We evaluated the effect of age-related gene expression signature on ALL treatment outcomes.
resultsSeven ALL drugs (asparaginase, prednisolone, mercaptopurine, dasatinib, nelarabine, daunorubicin, and inotuzumab ozogamicin) showed differential activity between children and adults, of which six were explained by age-related differences in leukemia molecular subtypes. Adolescents and young adults showed similar patterns of drug resistance as older adults, relative to young children. Mercaptopurine exhibited subtype-independent greater sensitivity in children. Transcriptomic profiling uncovered subclusters within
conclusionOur results provide pharmacogenomic insights into age-related disparities in ALL cure rates and identify leukemia prognostic features for treatment individualization across age groups.
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