Morphologic and Molecular Characteristics of De Novo AML With V617F Mutation.

V617F mutation (mut) in acute myeloid leukemia (AML) is rare. We describe the clinicopathologic findings of a single-institution series of 11 de novo AML cases with V617. We identified cases of de novo AML with V617F over a 10-year period. We reviewed diagnostic peripheral blood and bone marrow (BM) morphologic, cytogenetic, and molecular studies, including next-generation sequencing. The control group consisted of 12 patients with wild-type (wt) AML matched for age, sex, and diagnosis. We identified 11 patients (0.5%) with V617F, with a median age at diagnosis of 72.5 years (range, 36-90 years). Ten neoplasms were classified as AML with myelodysplasia-related changes and 1 as AML with t(8;21)(q22;q22). All mut AML cases showed at least bilineage dysplasia, 7 of 11 showed fibrosis, 8 of 11 had an abnormal karyotype, and 5 had deletions or monosomy of chromosomes 5 and 7. Using the European LeukemiaNet (ELN) classification, 9 patients (82%) with mut AML were intermediate-2 and adverse risk. Cases of mut AML did not have mutations in other activating signaling pathways (=.013); 7 (64%) showed additional mutations in at least one gene involving DNA methylation and/or epigenetic modification. Patients with mut AML had a significantly higher median BM granulocyte percentage (12% vs 3.5%; =.006) and a higher frequency of ELN intermediate-2 and adverse risk cytogenetics (=.04) compared with those with wt AML. mut AML showed higher circulating blasts, but this difference was not significant (17% vs 5.5%; =not significant). No difference was seen in the median overall survival rate of patients with mut AML versus those with wt AML (14 vs 13.5 months, respectively). De novo mut AML is rare and frequently found in patients with dysplasia, BM fibrosis, and abnormal karyotype with intermediate- or high-risk features; gene mutations in DNA methylation and epigenetic-modifying pathways; and absence of gene mutations in activating signaling pathways.