Table 2.

A summary of generated AML Zebrafish models and their contribution to the understanding of the disease.

Zebrafish Model	Zebrafish Manipulation	Model Features and Major Findings	References
spi-1: MYST3/NCOA2-EGFP	Transgenic expression of human MYST3/NCOA2 fusion under the spi-1/pu.1 promoter	First AML model in zebrafish 1.1% of transgenic fishes expressing the transgene developed AML after long latency	[29]
hsp70: AML1-ETO	Transgenic expression of human AML1-ETO fusion under hsp70 promoter	A phenotype similar to human AML Disruption of definitive hematopoiesis: the switch of cell fates from erythroid to myeloid through gata1 downregulation and pu.1 overexpression AML1-ETOs effects on HPCs differentiation was mediated through Cycloxygenase-2 (COX-2) and β-catenin signaling pathways	[36,37]
mRNA: NPMc+	mRNAs injection into 1-cell–stage embryos followed by morpholinos (MOs) targeting npm1a and npm1b	Perturbation of primitive and definitive hematopoiesis Alterations in the expression of major transcription factors (pu.1+, mpx+, csf1r+, c-myb, CD41, RUNX1)	[52]
HSE-MYCN-EGFP	Induction of murine N-myc gene through heat-shock promoter	AML development with high incidence and rapid onset Enhancement of primitive hematopoiesis through alteration of transcription factors (pu.1, gata1, scl, lmo2, p27kip and p21cip1) Activation of major cancer signaling pathways	[41]
IDH1/2 mutants	Knockdown of zebrafish idh1 and idh2 (zidh1 and zidh2) by morpholino knockdown and Transcription activator-like effector nuclease (TALEN-)mediated mutagenesis	zidh1 suppression/deletion is correlated with a blockage of differentiation of the myeloid lineage zidh1 effects definitive hematopoiesis exclusively zidh2 affects primitive hematopoiesis exclusively	[63]
	Transgenic expression of human IDH1 mutation	Embryos recapitulated the features of human AML
FLT3-ITD-2A-EGFP spi-1: NPM1-Mut-PA spi-1:	Transgenic expression of human FLT3-ITD or/and NPM1 mutations under the spi-1 promoter	Myeloproliferative neoplasm (MPN) development as a result of a single mutation. 66.6% of double mutant transgenic fish showed increased precursor cells in the kidney marrow along with dedifferentiated myeloid blasts.	[53]
spi-1: CREB-EGFP	Expression of CREB-EGFP under spi-1 promoter in myeloid lineage	Alteration of primitive hematopoiesis in embryos AML development in 79% of adult fishes by 9–14 months Aberrant expression of 20 genes diagnosed in pediatric AML	[57]
Spi-1: SOX4-EGFP	Expression of SOX4 protein downstream the spi-1 promoter	Increase in the number of myeloid progenitor cells and blast cells in the kidney marrow Distortion of the kidney structure	[59]