 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Feb 12, 2024 |
| Title |
UBTF tandem duplication acute myeloid leukemias are sensitive to menin inhibition [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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
|
| |
|
| Contributor(s) |
Barajas JM, Klco JM |
| Citation(s) |
37890156 |
| |
| Submission date |
Apr 13, 2023 |
| Last update date |
Mar 31, 2024 |
| Contact name |
Guangchun Song |
| Phone |
901-595-5722
|
| Organization name |
St Jude Children's Research Hospital
|
| Department |
Pathology
|
| Lab |
Klco
|
| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (12)
|
| GSM7170135 |
RNA-seq in FKBP12 tagged UBTF-TD54 cbCD34+ cells treated with DMSO, C1 |
| GSM7170136 |
RNA-seq in FKBP12 tagged UBTF-TD54 cbCD34+ cells treated with DMSO, C2 |
| GSM7170137 |
RNA-seq in FKBP12 tagged UBTF-TD54 cbCD34+ cells treated with DMSO, C3 |
| GSM7170138 |
RNA-seq in FKBP12 tagged UBTF-TD54 cbCD34+ cells treated with dTAG-13, C4 |
| GSM7170139 |
RNA-seq in FKBP12 tagged UBTF-TD54 cbCD34+ cells treated with dTAG-13, C5 |
| GSM7170140 |
RNA-seq in FKBP12 tagged UBTF-TD54 cbCD34+ cells treated with dTAG-13, C6 |
| GSM7170141 |
RNA-seq of bone marrow cells from UBTF-TD PDX model treated with Veh, R15 |
| GSM7170142 |
RNA-seq of bone marrow cells from UBTF-TD PDX model treated with Veh, R16 |
| GSM7170143 |
RNA-seq of bone marrow cells from UBTF-TD PDX model treated with Veh, R17 |
| GSM7170144 |
RNA-seq of bone marrow cells from UBTF-TD PDX model treated with SNDX, R18 |
| GSM7170145 |
RNA-seq of bone marrow cells from UBTF-TD PDX model treated with SNDX, R19 |
| GSM7170146 |
RNA-seq of bone marrow cells from UBTF-TD PDX model treated with SNDX, R20 |
|
| This SubSeries is part of SuperSeries: |
| GSE229666 |
UBTF tandem duplication acute myeloid leukemias are sensitive to menin inhibition |
|
| Relations |
| BioProject |
PRJNA955243 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE229663_RNASeq_DTAG-DMSO_log2CPM.txt.gz |
461.1 Kb |
(ftp)(http) |
TXT |
| GSE229663_RNASeq_SNDX-Veh_log2CPM.txt.gz |
479.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...