This study investigates the genetic basis of myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis. The authors identified a 6.2-Mbp region on chromosome 9p that contains the Janus kinase 2 (JAK2) gene, which is frequently affected by loss of heterozygosity (LOH) in these disorders. They found a G→T transversion in the JAK2 gene, resulting in a V617F mutation, in all 51 patients with 9pLOH. This mutation is absent in healthy controls and other myeloproliferative disorders. The V617F mutation is a somatic mutation, likely caused by mitotic recombination, and confers a proliferative and survival advantage to hematopoietic cells. Patients with the V617F mutation had a longer disease duration and higher rates of complications compared to those without the mutation. The study suggests that the V617F mutation in JAK2 is a dominant gain-of-function mutation contributing to the clonal expansion in MPDs and could be a potential target for therapeutic intervention.This study investigates the genetic basis of myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis. The authors identified a 6.2-Mbp region on chromosome 9p that contains the Janus kinase 2 (JAK2) gene, which is frequently affected by loss of heterozygosity (LOH) in these disorders. They found a G→T transversion in the JAK2 gene, resulting in a V617F mutation, in all 51 patients with 9pLOH. This mutation is absent in healthy controls and other myeloproliferative disorders. The V617F mutation is a somatic mutation, likely caused by mitotic recombination, and confers a proliferative and survival advantage to hematopoietic cells. Patients with the V617F mutation had a longer disease duration and higher rates of complications compared to those without the mutation. The study suggests that the V617F mutation in JAK2 is a dominant gain-of-function mutation contributing to the clonal expansion in MPDs and could be a potential target for therapeutic intervention.