Sentinel mutations: the roses in the vineyard Comment

A central challenge in the care of patients with myeloproliferative neoplasms (MPNs) is identifying those individuals at high risk for transformation into acute leukemia, an exacerbation that carries a very poor prognosis.(1) In this issue of Blood, Marcault and colleagues(2) describe a novel type of mutation, for which I propose the term sentinel mutation (see figure). The acquisition of a sentinel mutation drastically increases the likelihood of leukemic transformation, even though in some patients the mutation does not occur in the cells that form the leukemic clone. Sentinel mutations function like roses planted in vineyards. Ailing flowers forecast the vines' impending infection with black rot or downy mildew as the roses are affected first, even if the species that blight the flowers differ slightly from those that spoil the grapes. Similarly, Marcault and colleagues have shown that patients with MPN that acquire mutations in the transcription factor nuclear factor erythroid 2 (NFE2) carry an increased risk of leukemic transformation, even though in some patients the mutations are not found in the leukemic cells.

Automated summary

The identification of sentinel mutations in MPN patients, which significantly increase the risk of leukemic transformation, even when not present in leukemic cells, is a crucial advancement in understanding and managing the disease. These mutations act as early indicators of potential disease progression, similar to canaries in a coal mine.