Insights into myelodysplastic syndromes from current preclinical models

Table 3 Published mouse models of myelodysplastic syndromes

Gene(s) studied	Model/technique	Tractability to human MDS								Ref.
		Anemia	Multi-lineage cytopenias	Dysplasia	Bone marrow cellularity	HSPC skewing	Secondary leukemia	Latency to leukemia	Survival
NUP98-HOXD13	Transgenic	Yes	Yes	Yes	Hyper-	Yes	Yes2	14 mo	-	[69]
Cd74-Nid67	Large scale chromosomal deletion, RPS14 haploinsufficient	Yes	No	Yes	Hypo-	Yes	No	-	1	[92]
SPARC	Knock-out	No	No	Yes	1	1	No	-	1	[97]
MIR-145, MIR146a	Retroviral transduction	No	No	Yes	1	1	Yes	4-14 mo	-	[143]
APC	Transgenic, haploinsufficient	Yes	No	Yes	1	Yes	No	-	3-8 mo	[99]
Csnk1a1	Transgenic, inducible	Yes	Yes	Yes	Yes	Yes	No	-	1	[94]
Srsf2	Transgenic, inducible	Yes	Yes	Yes	Normal	Yes	No	-	1	[98]
U2af1	Transgenic, inducible	No	No	No	Normal	Yes	No	-	-	[100]
Sf3b1	Transgenic, haploinsufficient	Yes	No	Yes	1	1	No	-	About 12 mo	[101]
RUNX1-D171N	Retroviral transduction	Yes	Yes	Yes	Normal to hyper-	1	Yes	4-13 mo	-	[105]
RUNX1-S291fsX300	Retroviral transduction	Yes	Yes	Yes	Normal to hyper-	1	Yes	4-13 mo	-	[105]
RUNX1S291fs/Ezh2	Retroviral transduction	Yes	Yes	Yes	Variable	1	No	-	262 d	[125]
Tet2	Transgenic, hypomorphic	Yes	Yes	Yes	Hyper-	Yes	No	-	11 mo	[115]
Tet2/Ezh2	Transgenic, inducible	Yes	Yes	Yes	Hyper-	Yes	No	-	10 mo	[141]
ASXL1	Transgenic, inducible	Yes	Yes	Yes	Hypo-	Yes	No	-	Median 50 wk	[122]
Asxl1	Transgenic, constitutive	Yes	Yes	Yes	Normal to hyper-	Yes3	16 mo	8-42 d	-	[123]
TERT	Transgenic, inducible	Yes	Yes	Yes	Hyper	Yes	Yes	1	12 mo	[124]
Evi1	Retroviral transduction	Yes	Yes	Yes	Hyper-	1	No	-	10-12 mo	[136]
SALL4	Transgenic	Yes	Yes	Yes	Hyper-	Yes	Yes	6 wk to 12 mo	-	[139]
Npm1	Transgenic, haploinsufficient	No	No	Yes	Hyper	No	Yes	24 mo	-	[138]
NRASD12-BCL2	Transgenic, inducible/constitutive	1	No	Yes	1	Yes	Yes	3-6 mo	-	[142]
Pten/Ship	Transgenic, Pten +/- Ship -/-	Yes	Yes	1	Hypo	Yes	No	-	5 wk	[140]
Dido	Knock-out	Yes	No	Yes	1	1	No	-	1	[137]
Arid4a	Knock-out	Yes	Yes	Yes	Hyper-	1	Yes	5 mo	-	[144]
Mll5	Knock-out	Yes	No	No	1	1	No	-	-	[145]

¹Denotes not reported, denotes not applicable;

²Some mice developed pre-T cell acute lymphoblastic leukemia;

³Only 1 of 18 mice developed AML. HSPC: Hematopoietic stem and progenitor cells; MDS: Myelodysplastic syndromes; AML: Acute myeloid leukemia.