Figure 3.

Patient-derived acute myeloid leukemia transplantation into GSS transgenic larvae increases leukemia-related disease mortality and shows increased clonal representation in comparison to control larvae. (A) Kaplan-Meier curve showing increased acute myeloid leukemia (AML)-related mortality in GSS larvae transplanted with each of four different patient-derived AML samples compared with casper control larvae transplanted with the same samples (P<0.0001). (B) Heatmap showing increased clonal representation in the GSS larvae compared to control larvae transplanted with the same sample as measured by RNA-error corrected sequencing. Different colors represent allele frequency from 0.002 (dark blue) to 1 (yellow). The white box represents an absence or allele frequency of less than 0.002. (C) Representative immunofluorescence images from sagittal zebrafish sections showing human CD33⁺ AML cells localized in the kidney marrow of the GSS transgenic fish. The left panel shows an overview of the fish section at 10x, and the white box highlights the region of interest. The top three right panels show images taken under normal exposure based on controls and the overexposed image shown in the middle of the lower three panels illustrates the kidney morphology. The parameters were kept constant between GSS and control sections during imaging (N=5). The yellow scale bar is equivalent to 100 μm, and the red scale bar is equivalent to 10 μm. The top panel shows images from kidney marrow of control larvae injected with human AML samples, where leukemia cells are not present, and the bottom shows GSS larvae with human CD33⁺ AML cells. Image specifications: 10x images: numerical aperture (NA) = 0.45; 63x images: NA = 1.4, Zoom = 1.5. GM-CSF/CSF: granulocyte-monocyte colony-stimulating factor/colony-stimulating factor; SCF/KITLG: stem cell factor/KIT ligand; CXCL12/ SDF1α:CXCL12/stromal cell derived factor 1α; GSS: GM-CSF/CSF, SCF/KITLG, CXCL12/SDF1α-expressing transgenic zebrafish.