|
| Status |
Public on Apr 20, 2020 |
| Title |
Targeting the scaffolding role of LSD1(KDM1A) poises acute myeloid leukemia cells for Retinoic Acid induced differentiation [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The histone demethylase LSD1 is deregulated in several tumors, including leukemias, providing the rationale for the clinical use of LSD1 inhibitors . In acute promyelocytic leukemia (APL), pharmacological doses of retinoic acid (RA) induce differentiation of APL cells through degradation of the PML-RAR oncogene. APL cells are resistant to LSD1 inhibition or knock-out, but LSD1 inhibition sensitizes them to physiological doses of RA without altering the stability of PML-RAR, and extends survival of leukemic mice upon RA treatment. Non-enzymatic activities of LSD1 are essential to block differentiation of leukemic cells, while the combination of LSD1 inhibitors (or LSD1 knock-out) with low doses of RA releases a differentiation-associated gene expression program, not strictly dependent on changes in histone H3K4 methylation (known substrate of LSD1). An integrated proteomic/epigenomic/mutational analysis showed that LSD1 inhibitors alter the recruitment of LSD1-containing complexes to chromatin through inhibition of the interaction between LSD1 and GFI1, a relevant transcription factor in hematopoiesis.
|
| |
|
| Overall design |
Examination of NB4 cells treated as indicated in each sample versus cells trated with DMSO (vehicle). MC_2580 = LSD1 inhibitor
|
| |
|
| Contributor(s) |
Ravasio R, Ceccacci E, Rossi P, Minucci S |
| Citation(s) |
32284990 |
| |
| Submission date |
Mar 19, 2019 |
| Last update date |
Apr 20, 2020 |
| Contact name |
Saverio Minucci |
| Organization name |
European Institute of Oncology
|
| Street address |
via Adamello 16
|
| City |
milano |
| ZIP/Postal code |
20139 |
| Country |
Italy |
| |
|
| Platforms (2) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (9)
|
|
| This SubSeries is part of SuperSeries: |
| GSE128530 |
Targeting the scaffolding role of LSD1(KDM1A) poises acute myeloid leukemia cells for Retinoic Acid induced differentiation |
|
| Relations |
| BioProject |
PRJNA528021 |
| SRA |
SRP188842 |
Less...
More...