The authors performed next-generation sequencing on samples from 49 patients with polycythemia vera (PV, n=24) or essential thrombocytosis (ET, n=25) who developed leukemic transformation to identify the associated candidate driver genes. Hierarchical classification identified three mutational groups associated with short-term, intermediate, and long-term transformation groups (median time to transformation, 3, 10, and 21 years, respectively). Mutations in RUNX1, IDH1/2, U2AF1, and TET2 were more frequent in the patients with short-term progression to acute leukemia, whereas mutations in TP53, NRAS, and BCORL1 were more frequent in patients with late transformation. At the time of leukemic transformation, TP53 was the most frequently identified molecular aberration (45%), often with a high variant allele frequency (>50%) or with a second mutation, suggesting loss of heterozygosity.
Genomic investigation of patients with ET or PV may aid in the identification of those at increased risk for leukemic transformation, particularly in patients harboring mutations in RUNX1, IDH1/2, U2AF1, and TET2. TP53 mutations were found in a significant portion of patients with late leukemic transformation, suggesting that these may represent clonal selection to treatment and/or require loss of heterozygosity.
– Curtis Lachowiez, MD
Essential thrombocythemia
Essential Thrombocythemia
Essentially Thrombocythemia (Exon 10)
