[Small molecular compounds for BCR/ABL-negative myeloproliferative neoplasms].

Since the identification of JAK2 V617F mutation in patients with BCR/ABL-negative myeloproliferative neoplasms in 2005, the molecular basis of these hematological disorders has been extensively studied. Consequently, various small molecular compounds including JAK2 inhibitors have been developed. The JAK2 inhibitor ruxolitinib improves survival as well as splenomegaly and the clinical symptomatic burden in intermediate-2 or high risk myelofibrosis patients. This agent also reduces the JAK2 V617F allele burden in some patients, suggesting that it also has a certain molecular effect. Based on the results of clinical studies, ruxolitinib has been approved for treatment of myelofibrosis in the United States and Europe. Clinical and preclinical studies of several other JAK2 inhibitors are currently ongoing. Other small molecular compounds including histone deacetylase inhibitors, mTOR inhibitors and telomerase inhibitors are currently being tested in clinical trials. We also discuss the possibility of combination therapies using JAK2 inhibitors and other agents.