Table 1.
Mouse models of AMKL and myelofibrosis
| Mouse model | Experimental approach | Comments | Reference |
|---|---|---|---|
| Myeloproliferative sarcoma virus | Infection of wild-type virus | BM and spleen fibrosis | 42 |
| TPO overexpression | Transgenic (APOE promoter) | Increased megakaryopoiesis but no overt myelofibrosis | 43 |
| TPO overexpression | Transgenic (IgH promoter) | Increased megakaryopoiesis accompanied by elevated TGF-β and myelofibrosis | 44 |
| TPO overexpression | Retroviral transduction and transplantation | BM and spleen fibrosis | 97 |
| GATA-1low | Deletion of gene regulatory elements | Aberrant megakaryopoiesis with gradual development of myelofibrosis | 57 |
| OTT-MAL translocation | Knock-in | Requires retroviral introduction of a MPLW515L to develop myelofibrosis | 55 |
| JAKT2875N mutation | Retroviral transduction and transplantation | Mixed characteristics of AMKL and MPN | 19 |
| JAK2V617F mutation | Transgenic | Depending on promoter, phenotype can resemble PV or ET; mice develop myelofibrosis | 49 |
| JAK2V617F mutation | Retroviral transduction and transplantation | Development of myelofibrosis was variable between mouse strains | 50 |
| JAK2V617F mutation | Retroviral transduction and transplantation | Myelofibrosis accompanied by osteosclerosis | 51 |
| JAK2V617F mutation | Knock-in | Splenomegaly with atypical MKs exhibiting emperipolesis; absence of fibrosis; resembles PV with evidence of thrombotic episodes | 47 |
| JAK2V617F mutation | Conditional knock-in | Similar features with JAK2V617F knock-in model but fibrosis is present; resembles PV | 48 |
| RBM6-CSF1R fusion protein | Retroviral transduction and transplantation | Variable phenotype; spleen reticulosis | 98 |
| MPLW515L mutation | Retroviral transduction and transplantation | BM reticulosis; rapidly lethal | 53 |
| MPLT487A mutation | Retroviral transduction and transplantation | Similar but less aggressive course to MPLW515L model | 54 |
| Ts65Dn mouse strain | Induced translocation resulting in segmental trisomy of distal chromosome 16 | Myelofibrosis after the first year of life | 58 |
| BACH1 | Transgenic | GATA-1 promoter drives expression; BACH1 mutation has not been reported in MPN | 99 |
| NF-E2 overexpression | Transgenic | Abnormally clustered MKs; increased deposition of collagen and reticulin | 100 |