Ruxolitinib is an effective treatment for CALR positive patients with myelofibrosis
Approximately 60 65% of patients with myelofibrosis carry mutations in the Janus kinase 2 gene (JAK2) and 5 10% carry mutations in the thrombopoietin receptor gene, MPL (Vainchenker et al, 2011) Recently, somatic mutations in the calreticulin gene (CALR) were identified in most patients lacking JAK2 or MPL mutations (Klampfl et al, 2013; Nangalia et al, 2013) In preclinical models, overexpression of CALR mutations resulted in cytokine independent proliferation of Ba/F3 cells and activation of signal transducer and activator 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 and symptoms in two patients with myelofibrosis (Passamonti et al, 2014) These results suggest that inhibition of abnormal JAK/STAT signalling represents a therapeutic option for CALR mutated patients.
British journal of haematology