Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia

Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515UK mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671 F mutation. MPLW515UK patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwV JAK2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factorformicrovesseldisturbances,suggest- ing platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwtlJAK2wt patients. MPLW515UK patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.