Elisabeth R. Wilson

Washington University in St. Louis

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

David H. Spencer

Washington University in St. Louis

Lisa Eidenschink Brodersen

Children's Hospital of Philadelphia

Denise A. Wells

Applied Biomathematics (United States)

Michael R. Loken

Applied Biomathematics (United States)

Todd A. Alonzo

University of Southern California

Laura Pardo

Hospital Pedro de Elizalde

Soheil Meshinchi

Fred Hutch Cancer Center

Andrew P. Voigt

University of Iowa

Andrew J. Menssen

Washington University in St. Louis

Barbara K. Zehentner

Massachusetts General Hospital

Cooperative Institutions

Washington University in St. Louis

Applied Biomathematics (United States)

Massachusetts General Hospital

University of Washington

Children's Oncology Group

St. Jude Children's Research Hospital

Fred Hutch Cancer Center

Alvin J. Siteman Cancer Center

University of Southern California

Barnes-Jewish Hospital

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Down Syndrome AML Is Unique in Phenotype Both at Diagnosis and in Post Chemotherapy Regeneration

Blood (2016)

Elisabeth R. Wilson Lisa Eidenschink Brodersen Barbara K. Zehentner Andrew J. Menssen Andrew P. Voigt

Immunophenotyping

Minimal Residual Disease

10.1182/blood.v128.22.1687.1687

Cite

Citations (4)

Phenotype in combination with genotype improves outcome prediction in acute myeloid leukemia: a report from Children’s Oncology Group protocol AAML0531

Haematologica (2017)

Andrew P. Voigt Lisa Eidenschink Brodersen Todd A. Alonzo Robert B. Gerbing Andrew J. Menssen

Diagnostic biomarkers can be used to determine relapse risk in acute myeloid leukemia, and certain genetic aberrancies have prognostic relevance. A diagnostic immunophenotypic expression profile, which quantifies the amounts of distinct gene products, not just their presence or absence, was established in order to improve outcome prediction for patients with acute myeloid leukemia. The immunophenotypic expression profile, which defines each patient's leukemia as a location in 15-dimensional space, was generated for 769 patients enrolled in the Children's Oncology Group AAML0531 protocol. Unsupervised hierarchical clustering grouped patients with similar immunophenotypic expression profiles into eleven patient cohorts, demonstrating high associations among phenotype, genotype, morphology, and outcome. Of 95 patients with inv(16), 79% segregated in Cluster A. Of 109 patients with t(8;21), 92% segregated in Clusters A and B. Of 152 patients with 11q23 alterations, 78% segregated in Clusters D, E, F, G, or H. For both inv(16) and 11q23 abnormalities, differential phenotypic expression identified patient groups with different survival characteristics (P

Immunophenotyping

Hematology

Clinical Significance

10.3324/haematol.2017.169029

Cite

Citations (24)

Focal disruption of DNA methylation dynamics at enhancers in IDH-mutant AML cells

Leukemia (2021)

Elisabeth R. Wilson Nichole Helton Sharon E. Heath Robert S. Fulton Jacqueline E. Payton

Abstract Recurrent mutations in IDH1 or IDH2 in acute myeloid leukemia (AML) are associated with increased DNA methylation, but the genome-wide patterns of this hypermethylation phenotype have not been comprehensively studied in AML samples. We analyzed whole-genome bisulfite sequencing data from 15 primary AML samples with IDH1 or IDH2 mutations, which identified ~4000 focal regions that were uniquely hypermethylated in IDH mut samples vs. normal CD34+ cells and other AMLs. These regions had modest hypermethylation in AMLs with biallelic TET2 mutations, and levels of 5-hydroxymethylation that were diminished in IDH and TET -mutant samples, indicating that this hypermethylation results from inhibition of TET-mediated demethylation. Focal hypermethylation in IDH mut AMLs occurred at regions with low methylation in CD34+ cells, implying that DNA methylation and demethylation are active at these loci. AML samples containing IDH and DNMT3A R882 mutations were significantly less hypermethylated, suggesting that IDH mut -associated hypermethylation is mediated by DNMT3A. IDH mut -specific hypermethylation was highly enriched for enhancers that form direct interactions with genes involved in normal hematopoiesis and AML, including MYC and ETV6 . These results suggest that focal hypermethylation in IDH -mutant AML occurs by altering the balance between DNA methylation and demethylation, and that disruption of these pathways at enhancers may contribute to AML pathogenesis.

IDH2

DNA demethylation

Bisulfite sequencing

10.1038/s41375-021-01476-y

Cite

Citations (24)

Deciphering the Significance of CD56 Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Cytometry Part B Clinical Cytometry (2019)

Laura Pardo Andrew P. Voigt Todd A. Alonzo Elisabeth R. Wilson Robert B. Gerbing

Background In patients with acute myeloid leukemia (AML), CD56 expression has been associated with adverse clinical outcome. We reported on a phenotype associated with very poor prognosis (RAM) in children enrolled in the Children's Oncology Group trial AAML0531 (Brodersen et al. Leukemia 30 (2016) 2077–2080). RAM is also characterized in part by high‐intensity expression of the CD56 antigen. Herein, we investigate underlying biological and clinical differences among CD56‐positive AMLs for patients in AAML0531. Methods For 769 newly diagnosed pediatric patients with de novo AML enrolled in AAML0531, bone marrow specimens were submitted for flow cytometric analysis. For each patient, an immunophenotypic expression profile (IEP) was defined by mean fluorescent intensities of assayed surface antigens. Unsupervised hierarchical clustering analysis (HCA) was completed to group patients with similar immunophenotypes. Clusters were then evaluated for CD56 expression. Principal component analysis (PCA) was subsequently applied to determine whether CD56‐positive patient groups were nonoverlapping. Results HCA of IEPs revealed three unique phenotypic clusters of patients with CD56‐positive AML, and PCA showed that these three cohorts are distinct. Cohort 1 ( N = 77) showed a prevalence of t(8;21) patients (72%), Cohort 2 ( N = 52) a prevalence of 11q23 patients (69%), and Cohort 3 (RAM) ( N = 16) a prevalence of patients with co‐occurrence of the CBFA2T3–GLIS2 fusion transcript (63%). The 5‐year event‐free survival (EFS) for Cohorts 1, 2, and 3 were 69, 39, and 19%, respectively. Conclusions When leukemia is considered by its multidimensional immunophenotype and not by the expression of a single antigen, correlations are seen between genotype and there are significant differences in patient outcomes. © 2019 International Clinical Cytometry Society

Immunophenotyping

10.1002/cyto.b.21829

Cite

Citations (20)

ML-DS: A Unique Condition for Measurable Residual Disease Detection

Springer eBooks (2018)

Elisabeth R. Wilson R. Spencer Tong

Immunophenotyping

Minimal Residual Disease

Limiting

10.1007/978-3-319-94827-0_5

Cite

Citations (0)

Contribution of CTCF binding to transcriptional activity at the HOXA locus in NPM1-mutant AML cells

Leukemia (2020)

Reza Ghasemi Heidi Struthers Elisabeth R. Wilson David H. Spencer

Transcriptional regulation of the HOXA genes is thought to involve CTCF-mediated chromatin loops and the opposing actions of the COMPASS and Polycomb epigenetic complexes. We investigated the role of these mechanisms at the HOXA cluster in AML cells with the common NPM1c mutation, which express both HOXA and HOXB genes. CTCF binding at the HOXA locus is conserved across primary AML samples, regardless of HOXA gene expression, and defines a continuous chromatin domain marked by COMPASS-associated histone H3 trimethylation in NPM1-mutant primary AML samples. Profiling of the three-dimensional chromatin architecture in primary AML samples with the NPM1c mutation identified chromatin loops between the HOXA cluster and loci in the SNX10 and SKAP2 genes, and an intergenic region located 1.4 Mbp upstream of the HOXA locus. Deletion of CTCF binding sites in the NPM1-mutant OCI-AML3 AML cell line reduced multiple long-range interactions, but resulted in CTCF-independent loops with sequences in SKAP2 that were marked by enhancer-associated histone modifications in primary AML samples. HOXA gene expression was maintained in CTCF binding site mutants, indicating that transcriptional activity at the HOXA locus in NPM1-mutant AML cells may be sustained through persistent interactions with SKAP2 enhancers, or by intrinsic factors within the HOXA gene cluster.

CTCF

10.1038/s41375-020-0856-3

Cite

Citations (22)

Genome-wide analysis of focal DNA hypermethylation inIDH-mutant AML samples

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Elisabeth R. Wilson Nichole Helton Sharon E. Heath Robert S. Fulton Jacqueline E. Payton

Abstract Recurrent mutations in IDH1 or IDH2 in acute myeloid leukemia (AML) are associated with increased DNA methylation, but the genome-wide patterns of this hypermethylation phenotype have not been comprehensively studied in AML samples. We analyzed whole-genome bisulfite sequencing data from 15 primary AML samples with IDH1 or IDH2 mutations, which identified ~4,000 focal regions that were uniquely hypermethylated vs. normal CD34+ cells. These regions had modest, but significant, hypermethylation in AMLs with biallelic TET2 mutations, and 5-hydroxymethylation levels that were dependent on functional TET2, indicating that hypermethylation in these regions is caused by inhibition of TET-mediated demethylation. Focal hypermethylation in IDH mut AMLs occurred in regions with low methylation in normal CD34+ cells, implying that DNA methylation and demethylation are active at these loci. AML samples containing IDH and DNMT3A R882 mutations were significantly less hypermethylated, suggesting that methylation in these regions is mediated by DNMT3A. IDH mut -specific hypermethylation was highly enriched for enhancers that form direct interactions with genes involved in normal hematopoiesis and AML, including MYC and ETV6 . These results suggest that focal hypermethylation in IDH -mutant AML occurs by altering the balance between DNA methylation and demethylation, and that disruption of these pathways at enhancers may contribute to AML pathogenesis.

IDH2

DNA demethylation

Bisulfite sequencing

10.1101/2021.03.03.433799

Cite

Citations (0)

The impact of Down syndrome‐specific non‐malignant hematopoietic regeneration in the bone marrow on the detection of leukemic measurable residual disease

Cytometry Part B Clinical Cytometry (2023)

Fan‐Chi Hsu Chad A. Hudson Elisabeth R. Wilson Laura Pardo Timothy P. Singleton

Detection of measurable residual disease detection (MRD) by flow cytometry after the first course of chemotherapy is a standard measure of early response in patients with acute myeloid leukemia (AML). Myeloid leukemia associated with Down Syndrome (ML-DS) is a distinct form of AML. Differences in steady-state and regenerating hematopoiesis between patients with or without DS are not well understood. This understanding is essential to accurately determine the presence of residual leukemia in patients with ML-DS.A standardized antibody panel defined quantitative antigen expression in 115 follow-up bone marrow (BM) aspirates from 45 patients following chemotherapy for ML-DS or DS precursor B-cell acute lymphoblastic leukemia (B-ALL-DS) with the "difference from normal (ΔN)" technique. When possible, FISH and SNP/CGH microarray studies were performed on sorted cell fractions.93% of BM specimens submitted post chemotherapy had a clearly identifiable CD34+ CD56+ population present between 0.06% and 2.6% of total non-erythroid cells. An overlapping CD34+ HLA-DRheterogeneous population was observed among 92% of patients at a lower frequency (0.04%-0.8% of total non-erythroid cells). In B-ALL-DS patients, the same CD34+ CD56+ HLA-DRheterogeneous expression was observed. FACS-FISH/Array studies demonstrated no residual genetic clones in the DS-specific myeloid progenitor cells.Non-malignant myeloid progenitors in the regenerating BM of patients who have undergone chemotherapy for either ML-DS or B-ALL-DS express an immunophenotype that is different from normal BM of non-DS patients. Awareness of this DS-specific non-malignant myeloid progenitor is essential to the interpretation of MRD by flow cytometry in patients with ML-DS.

Immunophenotyping

Minimal Residual Disease

Induction chemotherapy

10.1002/cyto.b.22118

Cite

Citations (6)

KDM6B protects T-ALL cells from NOTCH1-induced oncogenic stress

Leukemia (2023)

Nancy Issa Hassan Bjeije Elisabeth R. Wilson Aishwarya Krishnan Wangisa M.B. Dunuwille

Demethylase

10.1038/s41375-023-01853-9

Cite

Citations (6)

Contribution of CTCF binding to transcriptional activity at the HOXA locus in NPM1-mutant AML cells

bioRxiv (Cold Spring Harbor Laboratory) (2020)

Reza Ghasemi Heidi Struthers Elisabeth R. Wilson David H. Spencer

Abstract Transcriptional regulation of the HOXA genes is thought to involve CTCF-mediated chromatin loops and the opposing actions of the COMPASS and Polycomb epigenetic complexes. We investigated the role of these mechanisms at the HOXA cluster in AML cells with the common NPM1c mutation, which express both HOXA and HOXB genes. CTCF binding at the HOXA locus is conserved across primary AML samples, regardless of HOXA gene expression, and defines a continuous chromatin domain marked by COMPASS-associated histone H3 trimethylation in NPM1 -mutant primary AML samples. Profiling of the three-dimensional chromatin architecture of NPM1 -mutant OCI-AML3 cells identified chromatin loops between the active HOXA9 - HOXA11 genes and loci in the SNX10 gene and an intergenic region located 1.4Mbp upstream of the HOXA locus. Deletion of CTCF binding sites in OCI-AML3 cells reduced these interactions, but resulted in new, CTCF-independent loops with regions in the SKAP2 gene that were marked by enhancer-associated histone modifications in primary AML samples. HOXA gene expression was maintained in the CTCF deletion mutants, indicating that transcriptional activity at the HOXA locus in NPM1 -mutant AML cells does not require long-range CTCF-mediated chromatin interactions, and instead may be driven by intrinsic factors within the HOXA gene cluster.

CTCF

10.1101/2020.02.17.952390

Cite

Citations (2)