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| Status |
Public on Dec 17, 2020 |
| Title |
Transcriptomic effects of combination Menin-MLL1 inhibition and FLT3 inhibition on human AML cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Chromosomal translocations of the MLL1 gene cooccur with the activating mutations in FLT3 kinase in acute myeloid leukemia patients, providing the rationale to explore combination of the menin-MLL1 inhibitor (MI-3454) and FLT3 inhibitor (Gilteritinib) in leukemia models. Here, we pursued global gene expression studies after 7 days of treatment of MOLM13 cells (harboring MLL-AF9 and FLT3-ITD) with MI-3454 and Gilteritinib used as single agents and in combination. We observed that MYC, differentiation and stemness-associated gene programs were disrupted by the single agent treatments, but the effect was enhanced upon combinatorial treatment. These results provide a mechanistic input on the increased activity of MI-3454 when combined with Gilteritinib in leukemia models versus single agent treatment.
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| Overall design |
Total RNA was prepared from MOLM13 cells treated for 8 days with DMSO, MI-3454, Gilteritnib or combination of these two agents. Libraries were prepped from total RNA and sequenced. Differential expression was performed by comparing each single agent or combination treatment to DMSO separately, then comparing the overlap of differentially expressed genes.
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| Contributor(s) |
Grembecka J, Cierpicki T, Ropa J |
| Citation(s) |
33331926 |
| |
| Submission date |
Apr 21, 2020 |
| Last update date |
Dec 17, 2020 |
| Contact name |
James Ropa |
| E-mail(s) |
jropa@iu.edu
|
| Organization name |
Indiana University
|
| Street address |
950 W Walnut St
|
| City |
Indianapolis |
| State/province |
IN |
| ZIP/Postal code |
46202 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA627203 |
| SRA |
SRP257762 |
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