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SRX19960031: GSM7170145: RNA-seq of bone marrow cells from UBTF-TD PDX model treated with SNDX, R19; Homo sapiens; RNA-Seq
1 ILLUMINA (Illumina NovaSeq 6000) run: 99.6M spots, 19.9G bases, 2.6Gb downloads

External Id: GSM7170145_r1
Submitted by: Klco, Pathology, St Jude Children's Research Hospital
Study: UBTF tandem duplication acute myeloid leukemias are sensitive to menin inhibition [RNA-seq]
show Abstracthide Abstract
UBTF tandem duplications (TD) have recently emerged as a subtype-defining alteration in pediatric acute myeloid leukemia (pAML), which is characterized by HOXB gene dysregulation and a poor response to conventional chemotherapy. Here, we use protein-protein interaction studies to show that UBTF-TD maintains interactions with components of the RNA pol I complex, while also engaging with a network of unique protein interactors specific to UBTF-TD, like KMT2A. These data suggest that UBTF- TD both preserves canonical UBTF functions and demonstrates gain of function activities. Furthermore, we show that UBTF-TD and KMT2A co-localize to key genomic targets dysregulated in UBTF-TD myeloid malignancies, like HOXB gene clusters and MEIS1. Using a protein degradation system, we show that stemness, proliferation, and the HOXB molecular signature are dependent on sustained UBTF-TD localization to chromatin. Finally, we show UBTF-TD leukemias are sensitive to menin inhibition—providing a viable therapeutic strategy for children with this high-risk AML subtype. Overall design: Comparative gene expression profiling analysis of RNA-seq data for cbCD34+ cells expressing FKBP12-F36V-tagged UBTF-TD treated with DMSO or dTAG-13, or human bone marrow cells isolated from UBTF-TD PDX model treated with Veh or SNDX-5613
Sample: RNA-seq of bone marrow cells from UBTF-TD PDX model treated with SNDX, R19
SAMN34172497 • SRS17307646 • All experiments • All runs
Organism: Homo sapiens
Library:
Name: GSM7170145
Instrument: Illumina NovaSeq 6000
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: RNA was harvested using Quikc-RNA Miniprep Kit (Zymo Research R1055)). RNA was then quantified using the Quant-iT RiboGreen RNA assay (ThermoFisher) and quality checked by the 2100 Bioanalyzer RNA 6000 Nano assay (Agilent) or 4200 TapeStation High Sensitivity RNA ScreenTape assay (Agilent) prior to library generation. Libraries were prepared from total RNA with the TruSeq Stranded Total RNA Library Prep Kit according to the manufacturer's instructions (Illumina, PN 20020599). Libraries were analyzed for insert size distribution using the 2100 BioAnalyzer High Sensitivity kit (Agilent), 4200 TapeStation D1000 ScreenTape assay (Agilent), or 5300 Fragment Analyzer NGS fragment kit (Agilent). Libraries were quantified using the Quant-iT PicoGreen ds DNA assay (ThermoFisher) or by low pass sequencing with a MiSeq nano kit (Illumina). Paired end 100 cycle sequencing was performed on a NovaSeq 6000 (Illumina).
Runs: 1 run, 99.6M spots, 19.9G bases, 2.6Gb
Run# of Spots# of BasesSizePublished
SRR2416202199,608,18119.9G2.6Gb2024-02-14

ID:
27336970

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