Blood cancers are a complex group of neoplasms caused by genetic mutations that result in the uncontrolled production of blood cells typically with reduced and/or aberrant function. Amongst the gene mutations, some trigger the onset of cancer while others facilitate its progression. Accordingly, hyperactivating mutations in granulocyte-colony stimulating factor receptor (G-CSFR) have been identified as drivers of some myeloid blood cancers while loss-of-function mutations in Runt-related transcription factor 1 (RUNX1) appear to co-operate with these mutations. However, the precise impact of these mutations on hematopoiesis is not completely understood. Our laboratory has previously generated a hyperactivating mutant of the zebrafish G-CSFR which increased the proliferation of embryonic neutrophils but without any overt signs of blood cancer. Therefore, this study aims to create a preclinical animal model using zebrafish that replicates mutations of G-CSFR and RUNX1 found in blood cancer patients to understand their collective impact on cancer progression. Accordingly, this project has used CRISPR/Cas9 gene editing to generate a loss-of function mutation in zebrafish RUNX1 on the G-CSFR mutant line creating a double mutant model. This is then comprehensively analyzed using common cellular markers to understand the interactions between the two genes. Current results have revealed that the cooperation of G-CSFR and RUNX1 leads to an alteration in immune cell numbers which is a characteristic of blood cancer. However, further studies are warranted to understand the precise impact of these gene mutations in blood cancer, which could be then used as a model for testing potential therapeutics for treating specific constellations of gene mutations.