Charlie Hatton

CRISPR base editor screening identifies spectrum of MEN1 mutations impacting menin inhibitors in clinical trials

Wallace Bourgeois, Hannah E. Rice, Daniela V. Wenge, Florian Perner et autres

Menin inhibitors have entered clinical trials for histone lysine methyltransferase 2 A (KMT2A)-rearranged and nucleophosmin 1 (NPM1)-mutant acute leukemias and are demonstrating promising activity. CRISPR base editor screening previously predicted several MEN1 (menin) mutations that have arisen in patients receiving SNDX-5613 and …

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High-throughput ligand diversification to discover chemical inducers of proximity

James B. Shaum, Miquel Muñoz i Ordoño, Erica Steen, Daniela V. Wenge et autres

Abstract Chemical inducers of proximity (CIPs) stabilize biomolecular interactions, often causing an emergent rewiring of cellular biochemistry. While the discovery of heterobifunctional CIPs is expedited by rational design strategies, molecular glues have relied predominantly on serendipity. We hypothesized that preexisting ligands could …

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Supplementary Tables S1-S14 from Mutant NPM1 Directly Regulates Oncogenic Transcription in Acute Myeloid Leukemia

Hannah J. Uckelmann, Elena L. Haarer, Reina Takeda, Eric M. C. Wong et autres

Table S1. Read normalized ratios of ChIPseq signal of untreated versus dTAG-13 treated OCI-AML3-NPM1c-FKBP12 cells.Table S2. Summary of NPM1c and NPM1 Chromatin Binding Targets.Table S3. Patient info for patient derived xenograft (PDX) models used.Table S4. ChIPseq reads per kilobase (rpk) data summary …

Supplementary Figures S1-S12 from Mutant NPM1 Directly Regulates Oncogenic Transcription in Acute Myeloid Leukemia

Hannah J. Uckelmann, Elena L. Haarer, Reina Takeda, Eric M. C. Wong et autres

Supplementary Figure 1. NPM1c degradation leads to differentiation of OCI-AML3 cells.Supplementary Figure 2. NPM1c chromatin targets identified in OCI-AML3-NPM1c-FKBP12 cells and validated by targeted degradation.Supplementary Figure 3. Motif analysis reveals developmental transcription factor binding sites at NPM1c bound regions.Supplementary Figure 4. NPM1c …

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Matthew L. Hemming, Morgan R. Benson, Michael A. Loycano, Justin A. Anderson et autres

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Matthew L. Hemming, Morgan R. Benson, Michael A. Loycano, Justin A. Anderson et autres

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Matthew L. Hemming, Morgan R. Benson, Michael A. Loycano, Justin A. Anderson et autres

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Matthew L. Hemming, Morgan R. Benson, Michael A. Loycano, Justin A. Anderson et autres

Abstract Gastrointestinal stromal tumor (GIST) is commonly characterized by activating mutations in the receptor tyrosine kinase KIT. Tyrosine kinase inhibitors are the only approved therapy for GIST, and complementary treatment strategies are urgently needed. As GIST lacks oncogene amplification and relies upon …

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Matthew L. Hemming, Morgan R. Benson, Michael A. Loycano, Justin A. Anderson et autres

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

Matthew L. Hemming, Morgan R. Benson, Michael A. Loycano, Justin A. Anderson et autres

Supplementary Data from MOZ and Menin–MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor

The KMT2A-PTD oncoprotein depends on ENL but not menin to drive AML gene expression

Daniela V. Wenge, Sydney R. Schweber, Meaghan Boileau, Christian Marinaccio et autres

Abstract Background: Partial tandem duplications of the histone methyltransferase KMT2Agene(KMT2A-PTD) are the most common KMT2A-aberration in adult acute myeloid leukemia (AML). KMT2A-PTD AML represents a high-risk disease subset with a poor prognosis. However, KMT2A-PTD leukemia is under studied, likely due to a …

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Supplementary Tables S1-S17 from KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia

Nicole Lynn Michmerhuizen, Emily Heikamp, Ilaria Iacobucci, Masayuki Umeda et autres

Supplementary Table S1. Exonic mutations/indels in Nup98::Kdm5a;Vav-Cre tumors developing after bone marrow transplant Supplementary Table S2. Exonic mutations/indels in spontaneous Nup98::Kdm5a;Vav-Cre tumors Supplementary Table S3. Enrichment/depletion of gRNAs for in vivo epigentic CRISPR/Cas9 screen Supplementary Table S4. Enrichment/depletion of genes for in …