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| Status |
Public on Nov 03, 2021 |
| Title |
p300 suppresses the transition of myelodysplastic syndrome to acute myeloid leukemia [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The p300 lysine acetyltransferase (KAT) can function as an oncogene or a tumor suppressor in hematologic malignancies. We have identified a tumor suppressor role for p300 in myelodysplastic syndrome (MDS) driven by Tet2 deficiency. Compared to Tet2-null hematopoietic stem and progenitor cells (HSPCs), HSPCs lacking both p300 and Tet2 (double knock out, DKO) displayed enhanced proliferation and impaired differentiation. Consequently, p300Δ/Δ Tet2-/- mice developed acute myeloid leukemia. p300 loss in Tet2-/- HSPCs induced a global epigenomic reprogramming that enhanced leukemogenicity at least in part by increasing expression of Myb, as knock-down of Myb specifically hindered the proliferation of the DKO HSPCs. We show that p300 KAT activity regulates the function of Tet2 null HSPCs, and that augmenting p300 function impairs their unlimited self-renewal. Such a strategy could prove useful in individuals with Tet2 deficient hematopoiesis or MDS.
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| Overall design |
RNAseq was performed on 1-2x10^5 sorted LSK cells from 8-10 week old Mx1-Cre+ WT, Ep300f/f, Tet2-/-, or Ep300f/f;Tet2-/- mice, 2 weeks after poly(I:C) injections.
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| |
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| Contributor(s) |
Man N, Nimer S |
| Citation(s) |
34622806 |
| |
| Submission date |
Feb 24, 2020 |
| Last update date |
Nov 03, 2021 |
| Contact name |
Stephen Nimer |
| Organization name |
University of Miami
|
| Department |
Sylvester Comprehensive Cancer Center
|
| Street address |
1120 NW 14th ST
|
| City |
Miami |
| State/province |
FL |
| ZIP/Postal code |
33136 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE145878 |
p300 suppresses the transition of myelodysplastic syndrome to acute myeloid leukemia |
|
| Relations |
| BioProject |
PRJNA608445 |
| SRA |
SRP250516 |
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