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

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. - In: BRITISH JOURNAL OF HAEMATOLOGY. - ISSN 1365-2141. - ELETTRONICO. - (2016), pp. 938-940. [10.1111/bjh.13644]

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

GUGLIELMELLI, PAOLA;BOGANI, COSTANZA;PROVENZANO, ALDESIA;GIGLIO, SABRINA RITA
2016

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
2016
938
940
Goal 3: Good health and well-being for people
Guglielmelli, Paola; Rotunno, Giada; Bogani, Costanza; Mannarelli, Carmela; Giunti, Laura; Provenzano, Aldesia; Giglio, Sabrina Rita
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1010589
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