Using gene expression and mutational profiling to characterize canine acute myeloid leukemia and assess their comparative features with human acute myeloid leukemia
Date
2023
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Abstract
Acute myeloid leukemia (AML) is an aggressive heterogenous hematopoietic neoplasm that afflicts both dogs and people. Over 10,000 individuals (about the seating capacity of Cameron basketball stadium at Duke University) in the United States succumb to AML-related deaths every year. Treatment options for AML have made little progress in the past few decades and prognosis for both human and canine AML (cAML) remains dismal. However, there are large ongoing multi-institutional studies devoted to advancing medical management for human AML (hAML) by providing targeted therapeutics to patients based on their molecular characteristics. A preclinical model for testing novel therapies could accelerate the development of better treatments in people. We hypothesize that cAML will have similar underlying molecular features as human AML and dogs could be a translational model for developing therapeutics focused on treating AML. The goals of this thesis were to assess the gene expression programs and mutational profiles of cAML and compare our findings with available human AML data. First, we established diagnostic criteria for defining cAML using flow cytometry. Next, we globally assessed normal hematopoiesis in dogs using single cell transcriptomics to generate a hematopoietic tree for defining the cellular composition of cAML. Additionally, we investigated the mRNA expression and genetic variants in cAML to ultimately compare the molecular features with pediatric and adult AML subtypes. We hope this work advances our knowledge of cAML molecular characteristics and adds further credentials to the dog as spontaneous model for human AML.
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Embargo expires: 08/28/2025.
Subject
CD34
gene expression
acute leukemia
myeloid
dog