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

GUGLIELMELLI, PAOLA;Rotunno, Giada;BOGANI, COSTANZA;Mannarelli, Carmela;Giunti, Laura;PROVENZANO, ALDESIA;GIGLIO, SABRINA RITA

Member of the Collaboration Group

2016-01-01

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Abstract

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 (Vainchenkeret al, 2011). Recently, somatic mutations in the calreticulin gene (CALR) were identified in most patients lacking JAK2 or MPL mutations (Klampflet al, 2013; Nangalia et al, 2013). In preclinical models, overexpression o fCALR mutations resulted in cytokine-independent prolifera-tion of Ba/F3 cells and activation of signal transducer and activator of transcription 5 (STAT5) (Klampflet 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.