TORNA ALL’ELENCO

Novel CALR somatic mutations in essential thrombocytemia in Haematologica

2015
AO Ordine Mauriziano

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (7)Vedi tutti...

Riera L

Osella-Abate S

Benevolo G


et alii...

Abstract

Essential Thrombocythemia (ET), Primary Myelofibrosis (PMF), and Polycythemia Vera (PV) are Philadelphia-negative (Ph-neg) classical myeloproliferative neoplasms (MPN). In 2005, diagnosis and treatment of Ph-neg MPNs were revolutionised by the discovery of the Janus Kinase 2 (JAK2) V617F mutation. Approximately 50-60% of ET patients harbored the JAK2V617F mutation while Thrombopoietin receptor (MPL) mutation was detected in 3-5% of cases. Recently, mutations in the Calreticulin (CALR) gene, encoding a multi-functional Ca2+ binding protein chaperone, were discovered in MPN patients. ET was characterised by thrombocytosis and absence of a relevant bone marrow fibrosis. In ET patients CALR mutations were associated with male gender, younger age, lower hemoglobin level and leukocyte count, higher platelet count and a reduced risk of thrombotic events. We retrospectively analysed JAK2, CALR and MPL mutations in 212 ET patients at the Section of Pathology of AO Città della Salute e della Scienza of Turin. The aim of this study was to provide additional details on the molecular characterisation of ET. JAK2, CALR and MPL mutations were detected in 51.4%, 28.3% and 3.8% of ET patients respectively. According to previous studies, CALR mutational frequency was 63% within both JAK2V617F and MPL W515L/K wild-type cases. The sequence characterisation of the 60 CALR mutated samples, showed a prevalence of type 1 (63.3%), followed by type 2 (20%), type 3 (5%) and type 14 (1.7%). The remaining 6 mutated cases (10%) consisted of 6 novel CALR mutations not yet described in COSMIC catalogue at March 2015. Despite the evidence that the resultant C-terminal is the same for all variants, different CALR mutations seem to correlate with clinical characteristics of the patients. As expected, in our series the male gender was associated with type 1 and younger age with type 2 variants. Furthermore, platelet count was significantly higher in type 2 vs type 1 mutated patients. Moreover,

Keywords

binding protein; thrombopoietin receptor; calreticulin; chaperone; Janus kinase 2; somatic mutation; thrombocythemia; society; hematology; mutation; patient; human; platelet count; gender; diagnosis; male; pH; risk; thrombocytosis; myeloid metaplasia; myeloproliferative neoplasm; prevalence; gene; wild type; pathology; female; leukocyte count; hemoglobin blood level; Philadelphia chromosome negative cell; myelofibrosis; polycythemia vera; phenotype; statistical significance; genotype; clinical feature; stratification;