|
| Status |
Public on Mar 19, 2014 |
| Title |
Expression analysis of Mll3 knockdown p53-/- HSPC vs. control p53-/- HSPC |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Recurring deletions of chromosome 7 and 7q [-7/del(7q)] occur in myelodysplastic syndromes and acute myeloid leukemia (AML) and are associated with poor prognosis. However, the identity of specific tumor suppressors on 7q remains elusive. Using RNAi and CRISPR/Cas9 approaches, we show that a ~50% reduction in gene dosage of the mixed lineage leukemia 3 (MLL3) gene, located on 7q36.1, cooperates with other events occurring in -7/del(7q) AMLs to promote leukemogenesis. Mll3 suppression impairs the differentiation of HSPC. Interestingly, Mll3 suppressed leukemias, like human -7/del(7q) AMLs, are refractory to conventional chemotherapy but sensitive to the BET inhibitor JQ1. Thus, our mouse model functionally validates MLL3 as a haploinsufficient 7q tumor suppressor, and suggests a therapeutic option for this aggressive disease.
|
| |
|
| Overall design |
Total RNA obtained from sorted lin-ckit+ hematopoietic stem and progenitor cells of recipient mice transplanted with shRen;p53-/- or shMll3;p53-/- cells at 6 weeks after transplant
|
| |
|
| Contributor(s) |
Chen C, Liu Y, Lowe SW |
| Citation(s) |
24794707 |
| Submission date |
Jan 22, 2014 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Chong Chen |
| E-mail(s) |
chen_chong@yahoo.com
|
| Organization name |
Sichuan University
|
| Department |
State Key Laboratory of Biotherapy
|
| Lab |
Chong Chen
|
| Street address |
17 Renmin S. Road-No. 3
|
| City |
Chengdu |
| State/province |
Sichuan |
| ZIP/Postal code |
610041 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA236139 |
Less...
More...