851P - Characterization of a zebrafish model of MYC-driven acute myeloid leukemia

Background

Acute myeloid leukemia (AML) is a clonal malignancy of the stem cell precursors of the myeloid lineage associate with uncontrolled proliferation and impaired differentiation of hematopoietic stem cells. Among the different genes found amplified in AML, the oncogene MYC is one of the prognostic factors with an impact of AML. Albeit MYC is a well know factor associated with the uncontrolled proliferation of AML, the mechanism that led to the oncogenesis established by MYC are not well known. Zebrafish has recently emerged as a valid model organism to study cancer development because of its genetic accessibility.

Methods

After the generation of a transgenic zebrafish line expressing the human MYC under the control of the neutrophils-specific promoter lysozyme (lyz:hMYC), we proceeded with FACS analysis of adult whole kidney marrow (WKM) of lyz:hMYC fish. Immunohistochemical analysis (IHC) of whole zebrafish was made to check the infiltration of cells and possible metastasis. May-Grunwald stain was made to check the kidney marrow population. Gene expression profile of WKM was performed to check the expression of genes associated with myc and its patthway. We conducted a Metagenomic analysis on possible variations in the intestinal microbiota associated with the disease causing its progression.

Results

FACS analysis of lyz:hMYC zebrafish revealed the expansion of myeloid cells with a significant reduction of erythroid cells, associated with anemia. The IHC analysis of whole lyz:hMYC zebrafish showed infiltration of myeloid cells into different organs confirming that those cells can proliferate unconditionally and metastasise. May-Grunwald analysis showed a higher number of blast cells unable to differentiate towards mature granulocytes in lyz:hMYC zebrafish than in their wild type siblings. The gene expression profile of WKM demonstrated the overexpression of exogenous MYC and of endogenous myc, suggesting a positive auto-regulation of MYC. Metagenomic analysis revealed that the gut microbes of AML fish were significantly altered with the possibility to be associated the progression of AML.

Conclusions

The model developed here is an excellent tool to further understand the mechanisms involved in MYC-induced AML and the relevance of gut microbiota on this disease.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University of Murcia.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.