William E. Evans
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View article: Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells
Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells Open
Somatic mitochondrial DNA (mtDNA) mutations are frequently observed in tumors, yet their role in pediatric cancers remains poorly understood. The heteroplasmic nature of mtDNA—where mutant and wild-type mtDNA coexist—complicates efforts to…
View article: Single-Cell Sequencing Reveals Extensive Genetic Diversity Underlying Pediatric ALL Treatment Complexity
Single-Cell Sequencing Reveals Extensive Genetic Diversity Underlying Pediatric ALL Treatment Complexity Open
Approximately 15-20% of children with acute lymphoblastic leukemia (pALL) are not cured despite years of treatment with more than ten chemotherapeutic agents, yet bulk sequencing reveals minimal somatic variation that could explain genetic…
View article: Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia
Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia Open
ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL) associated with favorable prognosis, but the optimal therapy for this subtype remains unclear. Profiling the genomic and pharmacological landscape o…
View article: Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia
Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia Open
Genomic alterations of IKZF1 are common and associated with adverse clinical features in B-ALL. The relationship between the type of IKZF1 alteration, disease subtype and outcome are incompletely understood. Leukemia subtype and genomic al…
View article: Data from Mutational Landscape and Patterns of Clonal Evolution in Relapsed Pediatric Acute Lymphoblastic Leukemia
Data from Mutational Landscape and Patterns of Clonal Evolution in Relapsed Pediatric Acute Lymphoblastic Leukemia Open
Relapse of acute lymphoblastic leukemia (ALL) remains a leading cause of childhood cancer-related death. Prior studies have shown clonal mutations at relapse often arise from relapse-fated subclones that exist at diagnosis. However, the ge…
View article: Bayesian modelling of response to therapy and drug-sensitivity in acute lymphoblastic leukemia
Bayesian modelling of response to therapy and drug-sensitivity in acute lymphoblastic leukemia Open
Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy involving the abnormal proliferation of immature lymphocytes, accounting for most pediatric cancer cases. ALL management in children has seen great improvement in…
View article: Prognostic and Pharmacotypic Heterogeneity of Hyperdiploidy in Childhood ALL
Prognostic and Pharmacotypic Heterogeneity of Hyperdiploidy in Childhood ALL Open
PURPOSE High hyperdiploidy, the largest and favorable subtype of childhood ALL, exhibits significant biological and prognostic heterogeneity. However, factors contributing to the varied treatment response and the optimal definition of hype…
View article: Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy
Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy Open
Vincristine is a widely used chemotherapeutic drug for the treatment of multiple malignant diseases that causes a dose-limiting peripheral neurotoxicity. There is no clinically effective preventative treatment for vincristine-induced senso…
View article: Supplementary Figures, and Supplementary Table Legends from Enhancer Hijacking Drives Oncogenic <i>BCL11B</i> Expression in Lineage-Ambiguous Stem Cell Leukemia
Supplementary Figures, and Supplementary Table Legends from Enhancer Hijacking Drives Oncogenic <i>BCL11B</i> Expression in Lineage-Ambiguous Stem Cell Leukemia Open
This file contains Supplementary Figures 1-23 with corresponding supplementary figure legends, as well as the legends for Supplementary Tables 1-15.
View article: Data from Enhancer Hijacking Drives Oncogenic <i>BCL11B</i> Expression in Lineage-Ambiguous Stem Cell Leukemia
Data from Enhancer Hijacking Drives Oncogenic <i>BCL11B</i> Expression in Lineage-Ambiguous Stem Cell Leukemia Open
Lineage-ambiguous leukemias are high-risk malignancies of poorly understood genetic basis. Here, we describe a distinct subgroup of acute leukemia with expression of myeloid, T lymphoid, and stem cell markers driven by aberrant allele-spec…
View article: Table S1 from <i>ARID5B</i> Influences Antimetabolite Drug Sensitivity and Prognosis of Acute Lymphoblastic Leukemia
Table S1 from <i>ARID5B</i> Influences Antimetabolite Drug Sensitivity and Prognosis of Acute Lymphoblastic Leukemia Open
Table S1 shows that downregulation of ARID5B led to more increases in LC50 of MTX and 6-MP than other antileukemic drugs
View article: Bayesian modelling of response to therapy and drug-sensitivity in acute lymphoblastic leukemia
Bayesian modelling of response to therapy and drug-sensitivity in acute lymphoblastic leukemia Open
Acute lymphoblastic leukemia (ALL) is a heterogeneous haematologic malignancy involving the abnormal proliferation of immature lymphocytes and accounts for most paediatric cancer cases. The management of ALL in children has seen great impr…
View article: <i>DPYD</i> Testing: Time to Put Patient Safety First
<i>DPYD</i> Testing: Time to Put Patient Safety First Open
In 2018, a patient received capecitabine without prior testing for dihydropyrimidine dehydrogenase (DPYD) and later presented with vomiting, rash, and diarrhea.The hospital failed to provide uridine triacetate in a timely fashion, and the …
View article: Epigenomic mapping in B-cell acute lymphoblastic leukemia identifies transcriptional regulators and noncoding variants promoting distinct chromatin architectures
Epigenomic mapping in B-cell acute lymphoblastic leukemia identifies transcriptional regulators and noncoding variants promoting distinct chromatin architectures Open
SUMMARY B-cell lineage acute lymphoblastic leukemia (B-ALL) is comprised of diverse molecular subtypes and while transcriptional and DNA methylation profiling of B-ALL subtypes has been extensively examined, the accompanying chromatin land…
View article: Functional investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment
Functional investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment Open
Although acute lymphoblastic leukemia (ALL) is the most common childhood cancer, there is limited understanding of the contribution of inherited genetic variation on inter-individual differences in chemotherapy response. Defining genetic f…
View article: <i>PACSIN2</i>as a modulator of autophagy and mercaptopurine cytotoxicity: mechanisms in lymphoid and intestinal cells
<i>PACSIN2</i>as a modulator of autophagy and mercaptopurine cytotoxicity: mechanisms in lymphoid and intestinal cells Open
PACSIN2 variants are associated with gastrointestinal effects of thiopurines and thiopurine methyltransferase activity through an uncharacterized mechanism that is postulated to involve autophagy. This study aims to clarify the role of PAC…
View article: Ex vivo Drug Sensitivity Imaging-based Platform for Primary Acute Lymphoblastic Leukemia Cells
Ex vivo Drug Sensitivity Imaging-based Platform for Primary Acute Lymphoblastic Leukemia Cells Open
Resistance of acute lymphoblastic leukemia (ALL) cells to chemotherapy, whether present at diagnosis or acquired during treatment, is a major cause of treatment failure. Primary ALL cells are accessible for drug sensitivity testing at the …
View article: Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients
Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients Open
Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which …
View article: Amino acid stress response genes promote L-asparaginase resistance in pediatric acute lymphoblastic leukemia
Amino acid stress response genes promote L-asparaginase resistance in pediatric acute lymphoblastic leukemia Open
Understanding the genomic and epigenetic mechanisms of drug resistance in pediatric acute lymphoblastic leukemia (ALL) is critical for further improvements in treatment outcomes. The role of transcriptomic response in conferring resistance…