Sylvia Tang
A5023232265- Acute Myeloid Leukemia Research
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Synthesis and biological activity
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Acute Lymphoblastic Leukemia research
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Lung Cancer Treatments and Mutations
- RNA Interference and Gene Delivery
- RNA Research and Splicing
University of Pennsylvania
2022-2024
Cancer Research Institute
2022-2024
The chromatin reader eleven-nineteen leukemia (ENL) has been identified as a critical dependency in acute myeloid (AML), but its therapeutic potential remains unclear. We describe potent and orally bioavailable small-molecule inhibitor of ENL, TDI-11055, which displaces ENL from by blocking YEATS domain interaction with acylated histones. Cell lines primary patient samples carrying MLL rearrangements or NPM1 mutations are responsive to TDI-11055. A CRISPR-Cas9-mediated mutagenesis screen...
Gain-of-function mutations in the histone acetylation "reader" eleven-nineteen-leukemia (ENL), found acute myeloid leukemia (AML) and Wilms tumor, are known to drive condensate formation gene activation cellular systems. However, their role tumorigenesis remains unclear. Using a conditional knock-in mouse model, we show that mutant ENL perturbs normal hematopoiesis, induces aberrant expansion of progenitors, triggers rapid onset aggressive AML. Mutant alters developmental inflammatory...
<p>Supplementary Figure S1. Generation of a conditional knock-in mouse model for the Enl-T1 mutation. Supplementary S2. Impact Enl mutation on peripheral blood and spleen. S3. Characterization allele expression concurrent mutations in heterozygous model. S4. UBC-cre-ERT2/Enl flox-T1/+ mice develop aggressive acute leukemia following tamoxifen treatment. S5. leads to expansion myeloid cells leukemic phase. S6. decrease B220+CD19+ B, CD4+T, CD8+ T S7. bone marrow, blood, spleen, thymus...
<div>Abstract<p>Gain-of-function mutations in the histone acetylation “reader” eleven-nineteen-leukemia (ENL), found acute myeloid leukemia (AML) and Wilms tumor, are known to drive condensate formation gene activation cellular systems. However, their role tumorigenesis remains unclear. Using a conditional knock-in mouse model, we show that mutant ENL perturbs normal hematopoiesis, induces aberrant expansion of progenitors, triggers rapid onset aggressive AML. Mutant alters...
<div>Abstract<p>Gain-of-function mutations in the histone acetylation “reader” eleven-nineteen-leukemia (ENL), found acute myeloid leukemia (AML) and Wilms tumor, are known to drive condensate formation gene activation cellular systems. However, their role tumorigenesis remains unclear. Using a conditional knock-in mouse model, we show that mutant ENL perturbs normal hematopoiesis, induces aberrant expansion of progenitors, triggers rapid onset aggressive AML. Mutant alters...
<p>Supplementary Figure S1. Generation of a conditional knock-in mouse model for the Enl-T1 mutation. Supplementary S2. Impact Enl mutation on peripheral blood and spleen. S3. Characterization allele expression concurrent mutations in heterozygous model. S4. UBC-cre-ERT2/Enl flox-T1/+ mice develop aggressive acute leukemia following tamoxifen treatment. S5. leads to expansion myeloid cells leukemic phase. S6. decrease B220+CD19+ B, CD4+T, CD8+ T S7. bone marrow, blood, spleen, thymus...
<div>Abstract<p>The chromatin reader eleven–nineteen leukemia (ENL) has been identified as a critical dependency in acute myeloid (AML), but its therapeutic potential remains unclear. We describe potent and orally bioavailable small-molecule inhibitor of ENL, TDI-11055, which displaces ENL from by blocking YEATS domain interaction with acylated histones. Cell lines primary patient samples carrying <i>MLL</i> rearrangements or <i>NPM1</i> mutations are...
Supplementary Data from Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia
Supplementary Data from Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia
Supplementary Data from Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia
Supplementary Data from Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia
Supplementary Data from Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia
Supplementary Data from Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia
<div>Abstract<p>The chromatin reader eleven–nineteen leukemia (ENL) has been identified as a critical dependency in acute myeloid (AML), but its therapeutic potential remains unclear. We describe potent and orally bioavailable small-molecule inhibitor of ENL, TDI-11055, which displaces ENL from by blocking YEATS domain interaction with acylated histones. Cell lines primary patient samples carrying <i>MLL</i> rearrangements or <i>NPM1</i> mutations are...
Abstract Acute myeloid leukemia (AML) is one of the most aggressive forms hematological malignancies with a low overall 5-year survival rate (&lt; 26%). The mainstay treatment for AML includes chemotherapy, but response subset patients to current options remains poor. Thus, new therapeutic approaches are desperately needed. often arises from somatic mutations in chromatin regulators that result uncontrolled proliferation and block differentiation progenitor cells. As such, investigation...