Abstract
Simple SummaryAcute myeloid leukemia (AML) accounts for 7.6% of hematopoietic malignancies with a long-term survival of less than 20%. Better understanding its physiopathology and finding new treatments remain important issues. In the current review, the authors discuss how genetic engineering technologies improvement allowed a better genetic characterization of AML. Such molecular dissection of the AML genome had two direct clinical impacts: a prognostic contribution by defining a new molecular classification of AML which guides therapeutic regimen intensity, and a therapeutic impact by allowing the identification of new therapeutic targets. New genome editing tools and animal models have also paved the way for a better understanding of AML leukemogenesis. Their impact is also summarized in this review. The combination of descriptive and functional genetics may ultimately be the key to improving the prognosis of this dismal disease.Over the past decades, genetic advances have allowed a more precise molecular characterization of AML with the identification of novel oncogenes and tumor suppressors as part of a comprehensive AML molecular landscape. Recent advances in genetic sequencing tools also enabled a better understanding of AML leukemogenesis from the preleukemic state to posttherapy relapse. These advances resulted in direct clinical implications with the definition of molecular prognosis classifications, the development of treatment recommendations based on minimal residual disease (MRD) measurement and the discovery of novel targeted therapies, ultimately improving AML patients’ overall survival. The more recent development of functional genomic studies, pushed by novel molecular biology technologies (short hairpin RNA (shRNA) and CRISPR-Cas9) and bioinformatics tools design on one hand, along with the engineering of humanized physiologically relevant animal models on the other hand, have opened a new genomics era resulting in a greater knowledge of AML physiopathology. Combining descriptive and functional genomics will undoubtedly open the road for an AML cure within the next decades.
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