TY - JOUR
T1 - Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia
AU - Vannucchi, Alessandro M.
AU - Antonioli, Elisabetta
AU - Guglielmelli, Paola
AU - Panerazzi, Alessandro
AU - Guerini, Vittoria
AU - Barosi, Giovanni
AU - Ruggeri, Marco
AU - Specchia, Giorgina
AU - Lo-Coco, Francesco
AU - Delaini, Federica
AU - Villani, Laura
AU - Finotto, Silvia
AU - Ammatuna, Emanuele
AU - Alterini, Renato
AU - Carrai, Valentina
AU - Capaccioli, Gloria
AU - Di Lollo, Simonetta
AU - Liso, Vincenzo
AU - Rambaldi, Alessandro
AU - Bosi, Alberto
AU - Barbui, Tiziano
PY - 2008/8/1
Y1 - 2008/8/1
N2 - Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the J4K2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/J4K2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellular ity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.
AB - Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the J4K2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/J4K2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellular ity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.
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U2 - 10.1182/blood-2008-01-135897
DO - 10.1182/blood-2008-01-135897
M3 - Article
C2 - 18519816
AN - SCOPUS:50949127379
VL - 112
SP - 844
EP - 847
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -