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| Status |
Public on Dec 23, 2018 |
| Title |
MLL-PTD and RUNX1-knockout cooperate to induce MDS phenotypes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The MLL-PTD mutation is found in patients with MDS and AML, and not in other hematological malignancies. Previously, we showed that Mll-PTD knock-in heterozygous mice (MllPTD/WT mice) present with several MDS-associated features. However, these phenotypes are insufficient to constitute bona fide MDS. MllPTD/WT mice do not generate MDS or AML in primary or transplant recipient mice. This suggests that additional genetic and/or epigenetic defects are necessary for transformation to MDS or AML. In secondary AML and de novo AML, MLL-PTD mutation is significantly associated with mutations in RUNX1 and with the FLT3-ITD mutations. In fact, the combination of MLL-PTD with the FLT3-ITD allele leads to AML in mice. We combined the MLL-PTD with RUNX1 mutant proteins, in order to generate a new mouse model for MDS. We generated MllPTD/WT/Runx1Flox/Flox/Mx1-Cre mice to model loss-of-function RUNX1 mutations. To test the significance of HIF-1α in this model, we also generated MllPTD/WT/Runx1Flox/Flox/Hif-1αFlox/Flox/Mx1-Cre mice and genetically eliminated Hif-1α expression. We analyzed gene expression variations in the HSPCs comparing the MllPTD/WT/Runx1∆/∆ with or without HIF-1α abrogation.
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| Overall design |
Expression profiles of mRNA in HSPCs from MLL-PTD/Runx1-KO mice with or without HIF-1α
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| Contributor(s) |
Hayashi Y, Chetal K, Salomonis N, Leighton Grimes H, Huang G |
| Citation(s) |
30139811 |
| |
| Submission date |
Sep 15, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Nathan Salomonis |
| E-mail(s) |
nathan.salomonis@cchmc.org
|
| Organization name |
Cincinnati Children's Hospital
|
| Department |
Biomedical Informatics
|
| Lab |
Nathan Salomonis
|
| Street address |
3333 Burnet Avenue
|
| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL15103 |
Illumina HiSeq 1000 (Mus musculus) |
|
| Samples (4)
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| Relations |
| BioProject |
PRJNA343076 |
| SRA |
SRP089915 |
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