| First Author | Kunter G | Year | 2011 |
| Journal | Exp Hematol | Volume | 39 |
| Issue | 12 | Pages | 1136-43 |
| PubMed ID | 21911095 | Mgi Jnum | J:189501 |
| Mgi Id | MGI:5445881 | Doi | 10.1016/j.exphem.2011.08.013 |
| Citation | Kunter G, et al. (2011) A truncation mutant of Csf3r cooperates with PML-RARalpha to induce acute myeloid leukemia in mice. Exp Hematol 39(12):1136-43 |
| abstractText | Severe congenital neutropenia is associated with a marked propensity to develop myelodysplasia or acute myeloid leukemia (AML). Truncation mutations of CSF3R, encoding the granulocyte colony-stimulating factor receptor (G-CSFR), are associated with development of myelodysplasia/AML in severe congenital neutropenia. However, a causal relationship between CSF3R mutations and leukemic transformation has not been established. Herein, we show that truncated G-CSFR cooperates with the PML-RARalpha oncogene to induce AML in mice. Expression of truncated G-CSFR significantly shortens the latency of AML in a G-CSF-dependent fashion and it is associated with a distinct AML presentation characterized by higher blast counts and more severe myelosuppression. Basal and G-CSF-induced signal transducer and activator of transcription 3, signal transducer and activator of transcription 5, and extracellular signal-regulated kinase 1/2 phosphorylation were highly variable but similar in leukemic blasts expressing wild-type and truncated G-CSFR. These data provide new evidence suggesting a causative role for CSF3R mutations in human AML. |
