Reversion to wild-type is not a common mechanism of progression from a JAK2-mutant myeloproliferative neoplasm to a JAK2 wild-type leukemia. (A) Mitotic recombination in a JAK2 V617F-heterozygous cell gives rise to both V617F-homozygous and JAK2 wild-type daughter cells, both of which harbor LOH for chromosome 9p. (B) Summary of SNP analysis in patients evolving to acute leukemia after a JAK2-mutant MPN, showing SNP locations relative to the JAK2 locus and genotyping results, whereas all informative JAK2 V617F-homozygous leukemias showed LOH close to JAK2, this was not observed in any of 9 JAK2 wild-type leukemias. Patient 1 is not included in this analysis because leukemic blasts were heterozygous for the JAK2 V617F mutation. SNP indicates single nucleotide polymorphism; hom, homozygous; and LOH, loss of heterozygosity.