Emerging Importance of Mutational Analysis in Myelodysplastic Syndrome and Acute Myelogenous Leukemia

Abstract

In 1956, the diploid number of chromosomes in humans was established as 46, opening the door for cytogeneticists to identify numerical and structural chromosome abnormalities that lead to human disease. Nearly 6 decades of critical discoveries describing the genetic underpinnings of leukemia have followed this watershed moment and provided drugable targets, including the Philadelphia chromosome, PML-RARA, and FLT3. The management of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) relies on cytogenetic analysis, because karyotype is a robust and independent predictor of outcome. For patients with MDS and AML, morphology alone is not sufficient, and cytogenetic analysis is an integral part of the diagnostic workup and disease monitoring. Despite modern karyotyping techniques, however, roughly half of patients with MDS and AML have a normal karyotype at diagnosis, leading to imprecise rendering of their disease. Somatic mutations identified via next-generation sequencing have emerged, taking us into a new phase of discovery and treatment for MDS and AML.