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

Among 994 patients with essential thrombocythemia (ET) who were genotyped for MPLW515L/K mutation 30 mutant patients (3.0%) were identified, 8 of whom also displayed the JAK2V671F mutation. MPLW515L/K patients presented lower hemoglobin level and higher platelet count than MPLwt; these differences were highly significant compared to MPLwt/JAK2V617F-positive patients. Reduced hemoglobin and increased platelet level were preferentially associated with W515L and W515K allele, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyper-reactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K mutant patients presented reduced total and erythroid bone marrow cellularity, whereas number of megakaryocytes, megakaryocytic clusters and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutation does not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.