Uniparental disomy may be associated with microsatellite instability in acute myeloid leukemia (AML) with a normal karyotype.

The discovery of underlying genetic lesions helps to better understand the mechanisms of leukemogenesis and identify prognostic subgroups. Recent insights have allowed normal karyotype acute myeloid leukemia (AML) to be split into many molecular entities according to the genetic status of FLT3, NPM, CEBPA and MLL. Genome-wide single nucleotide polymorphism analysis was performed on 22 well-characterised AML patients with a normal karyotype. At the same time, microsatellite instability was investigated using a commonly used panel of polymorphic markers. Loss of heterozygosity (LOH) was found in 22.7% of cases without an associated copy number variation, suggesting that LOH represented an acquired partial uniparental disomy (aUPD) event. Three UPD+ cases harboured NPM mutations, associated with FLT3-ITD in two of them. An additional UPD patient had mutations both in CEBPA and in WT1. MSI was present at three loci in the three UPD+ cases (60%), whereas single locus MSI was present in three UPD- patients (17%). MSI involved the polymorphic PIG3 promoter in two UPD+ cases. It remains to be tested whether UPD and MSI association marks a common pathway of leukemogenesis.