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 MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671F 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/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 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 cellularity, 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.
Unita Funzionale di Ematologia, Dipartimento di Area Critica Medico-Chirurgica, Università degli Studi, Florence, Italy. amvannucchi@unifi.it
Alessandro M
AM
Vannucchi
Elisabetta
E
Antonioli
Paola
P
Guglielmelli
Alessandro
A
Pancrazzi
Vittoria
V
Guerini
Giovanni
G
Barosi
Marco
M
Ruggeri
Giorgina
G
Specchia
Francesco
F
Lo-Coco
Federica
F
Delaini
Laura
L
Villani
Silvia
S
Finotto
Emanuele
E
Ammatuna
Renato
R
Alterini
Valentina
V
Carrai
Gloria
G
Capaccioli
Simonetta
S
Di Lollo
Vincenzo
V
Liso
Alessandro
A
Rambaldi
Alberto
A
Bosi
Tiziano
T
Barbui
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D015539:Platelet Activation; D010976:Platelet Count; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000097:blood / Q000235:genetics* / Q000473:pathology; D013927:Thrombosis
D006454:Hemoglobins; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D053614:Janus Kinase 2