committed to multiple hematopoietic lineages. 3 In contrast, Cambier et al provided evidence in another PV patient who developed CML that the PV and CML originated from distinct clones. 4 Our findings indicate that both the JAK2V617F mutation and BCR-ABL1 can occur concurrently in both CFU-GM and BFU-E and that JAK2V617F occurs before the acquisition of BCR-ABL1.The clinical phenotype of myeloproliferative neoplasms frequently evolves over time. Although this progression can be enhanced by the use of chemotherapeutic agents, it represents the natural clonal evolution of these malignancies. The development of CML in PV occurs much less frequently than myelofibrosis or acute myeloid leukemia, but should be considered in patients with PV who develop extreme leukocytosis. The contribution of BCR-ABL1 to disease progression appears to be greater than that of JAK2V617F, because these patients display a clinical phenotype that is consistent with CML rather than PV. These clinical observations represent an example of clonal evolution in which the initial genetic event is a mutation leading to the activation of a tyrosine kinase (JAK2), which is then followed by either a second genetic event leading to the acquisition of a fusion protein resulting in activation of another protein kinase (BCR-ABL1) or by homologous recombination resulting in JAK2V617F-homozygous HPCs that lack BCR-ABL1. Subsequently, the JAK2V617F-heterozygous HPCs with BCR-ABL1 can also undergo homologous recombination and become homozygous for JAK2V617F.