Table 1 Mouse models of AMKL and... | American Society of Hematology

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-1^low	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

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-1^low	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