| RRC ID |
67565
|
| 著者 |
Gavory G, Baril C, Laberge G, Bidla G, Koonpaew S, Sonea T, Sauvageau G, Therrien M.
|
| タイトル |
A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.
|
| ジャーナル |
PLoS Genet
|
| Abstract |
Acute myeloid leukemia (AML) underlies the uncontrolled accumulation of immature myeloid blasts. Several cytogenetic abnormalities have been associated with AML. Among these is the NUP98-HOXA9 (NA9) translocation that fuses the Phe-Gly repeats of nucleoporin NUP98 to the homeodomain of the transcription factor HOXA9. The mechanisms enabling NA9-induced leukemia are poorly understood. Here, we conducted a genetic screen in Drosophila for modifiers of NA9. The screen uncovered 29 complementation groups, including genes with mammalian homologs known to impinge on NA9 activity. Markedly, the modifiers encompassed a diversity of functional categories, suggesting that NA9 perturbs multiple intracellular events. Unexpectedly, we discovered that NA9 promotes cell fate transdetermination and that this phenomenon is greatly influenced by NA9 modifiers involved in epigenetic regulation. Together, our work reveals a network of genes functionally connected to NA9 that not only provides insights into its mechanism of action, but also represents potential therapeutic targets.
|
| 巻・号 |
17(8)
|
| ページ |
e1009730
|
| 公開日 |
2021-8-1
|
| DOI |
10.1371/journal.pgen.1009730
|
| PII |
PGENETICS-D-21-00368
|
| PMID |
34383740
|
| PMC |
PMC8384169
|
| MeSH |
Animals
Cell Differentiation / genetics
Drosophila melanogaster / genetics
Epigenesis, Genetic / genetics
Gene Expression / genetics
Gene Expression Regulation / genetics
Gene Regulatory Networks / genetics
Homeodomain Proteins / genetics*
Homeodomain Proteins / metabolism
Humans
Leukemia, Myeloid, Acute / genetics
Myeloid Cells / metabolism
Myeloid Cells / physiology
Nuclear Pore Complex Proteins / genetics*
Nuclear Pore Complex Proteins / metabolism
Oncogene Proteins, Fusion / genetics
Oncogene Proteins, Fusion / metabolism
Oncogenes / genetics
Transcription Factors / genetics
Translocation, Genetic / genetics
|
| IF |
5.175
|
| リソース情報 |
| ショウジョウバエ |
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