Abstract: Myelofibrosis is one of the BCR-ABL–negative clonal disorders that collectively are known as myeloproliferative neoplasms (MPNs). It is caused by the proliferation of clonal […]
Abstract: Polycythemia vera (PV) is a Philadelphia chromosome–negative chronic myeloproliferative neoplasm that is associated with a Janus kinase 2 (JAK2) mutation in most cases. The […]
H&O What is myelofibrosis? RM Myelofibrosis is a myeloproliferative neoplasm, a type of chronic leukemia. Myelofibrosis can evolve from an antecedent polycythemia vera or essential thrombocythemia, […]
H&O What are the characteristics of myelofibrosis? CH The cardinal features of the blood cancer myelofibrosis are splenomegaly, fibrosis in the marrow, and either myeloid proliferation […]
Abstract: The discovery of a common Janus kinase 2 (JAK2) point mutation, JAK2V617F, in myeloproliferative neoplasms has generated enormous interest in the development and therapeutic use of small molecule JAK2 inhibitor–targeted therapy in these diseases. A handful of compounds are currently in clinical development in primary myelofibrosis or post-polycythemia vera (PV)/essential thrombocythemia (ET) myelofibrosis. To date, clinical benefit has been demonstrated in terms of reduction of splenomegaly, improvement in constitutional symptoms, and control of leukocytosis. Some of the drugs have also been evaluated in PV and ET, with demonstrated activity against erythrocytosis, thrombocytosis, pruritus, and splenomegaly. However, drug effect on bone marrow fibrosis or JAK2 allele burden has been modest so far. Regardless, it is important to keep in mind that current anti-JAK2 treatment trials constitute only the beginning of many upcoming similar clinical trials, and that it is premature to make generalizations or any form of comparative conclusions regarding drug activity or toxicity.