Ruxolitinib is an effective treatment for CALR-positive patients with myelofibrosis

Approximately 60–65% of patients with myelofibrosis carrymutations in the Janus kinase 2 gene (JAK2) and 5–10Êrry mutations in the thrombopoietin receptor gene, MPL(Vainchenker et al, 2011). Recently, somatic mutations in thecalreticulin gene (CALR) were identified in most patientslacking JAK2 or MPL mutations (Klampfl et al, 2013; Nan-galia et al, 2013). In preclinical models, overexpression ofCALR mutations resulted in cytokine-independent prolifera-tion of Ba/F3 cells and activation of signal transducer andactivator of transcription 5 (STAT5) (Klampfl et al, 2013).Fedratinib, a JAK2 inhibitor, suppressed these effects in vitro(Klampfl et al, 2013) and reduced palpable spleen length andsymptoms in two patients with myelofibrosis (Passamontiet al, 2014). These results suggest that inhibition of abnormalJAK/STAT signalling represents a therapeutic option forCALR-mutated patients