Clinical Utility of Next-Generation Sequencing in Acute Myeloid Leukemia

AbstractAcute myeloid leukemia (AML) is a genetically heterogeneous disease that, even with current advancements in therapy, continues to have a poor prognosis. Recurrent somatic mutations have been identified in a core set of pathogenic genes includingFLT3 (25 –30% prevalence),NPM1 (25 –30%),DNMT3A (25 –30%),IDH1/2 (5 –15%), andTET2 (5 –15%), with direct diagnostic, prognostic, and targeted therapeutic implications. Advances in the understanding of the complex mechanisms of AML leukemogenesis have led to the development and recent US Food and Drug Administration (FDA) approval of several targeted therapies: midostaurin and gilte ritinib targeting activatedFLT3, and ivosidenib and enasidenib targeting mutatedIDH1/2. Several additional drug candidates targeting other recurrently mutated gene pathways in AML are also being actively developed. Furthermore, outside of the realm of predicting responses to targeted therapies, many other mutated genes, which comprise the so-called long tail of oncogenic drivers in AML, have been shown to provide clinically useful diagnostic and prognostic information for AML patients. Many of these recurrently mutated genes have also been shown to be excellent biomarkers for post-treatment minimal residual disease (MRD) monitoring for assessing treatment response and predicting future relapse. In addition, the identification of germline mutations in a set of genes predisposing to myeloid malignancies may directly inform treatment decisions...
Source: Molecular Diagnosis and Therapy - Category: Molecular Biology Source Type: research