Published online 16 July 2009
Haematologica, Vol 94, Issue 11, 1537-1545 doi:10.3324/haematol.2009.007047
Copyright © 2009 by Ferrata Storti Foundation
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Myeloproliferative Neoplasms

The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera

Lisa Pieri1,2, Costanza Bogani1,2, Paola Guglielmelli1,2, Maria Zingariello3, Rosa Alba Rana3, Niccolò Bartalucci1,2, Alberto Bosi1,2, Alessandro M. Vannucchi1,2

1 Unità Funzionale di Ematologia, Dipartimento di Area Critica, Università degli Studi, Firenze
2 Istituto Toscano Tumori, Firenze
3 Dipartimento di Biomorfologia, Università G. d’Annunzio Chieti-Pescara, Italy

Correspondence: Alessandro M. Vannucchi, MD, U.F. di Ematologia, Università degli Studi, 50134 Florence, Italy. E-mail:amvannucchi{at}unifi.it

Background: The JAK2V617F mutation has been associated with constitutive and enhanced activation of neutrophils, while no information is available concerning other leukocyte subtypes.

Design and Methods: We evaluated correlations between JAK2V617F mutation and the count of circulating basophils, the number of activated CD63+ basophils, their response in vitro to agonists as well as the effects of a JAK2 inhibitor.

Results: We found that basophil count was increased in patients with JAK2V617F -positive myeloproliferative neoplasms, particularly in those with polycythemia vera, and was correlated with the V617F burden. The burden of V617F allele was similar in neutrophils and basophils from patients with polycythemia vera, while total JAK2 mRNA content was remarkably greater in the basophils; however, the content of JAK2 protein in basophils was not increased. The number of CD63+ basophils was higher in patients with polycythemia vera than in healthy subjects or patients with essential thrombocythemia or primary myelofibrosis and was correlated with the V617F burden. Ultrastructurally, basophils from patients with polycythemia vera contained an increased number of granules, most of which were empty suggesting cell degranulation in vivo. Ex vivo experiments revealed that basophils from patients with polycythemia vera were hypersensitive to the priming effect of interleukin-3 and to f-MLP-induced activation; pre-treatment with a JAK2 inhibitor reduced polycythemia vera basophil activation. Finally, we found that the number of circulating CD63+ basophils was significantly greater in patients suffering from aquagenic pruritus, who also showed a higher V617F allele burden.

Conclusions: These data indicate that the number of constitutively activated and hypersensitive circulating basophils is increased in polycythemia vera, underscoring a role of JAK2V617F in these cells’ abnormal function and, putatively, in the pathogenesis of pruritus.

Key words: JAK2V617F mutation, basophil, polycythemia vera, pruritus.


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Francisco Cervantes, Eduardo Arellano-Rodrigo, Alberto Alvarez-Larrán
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F. Cervantes, E. Arellano-Rodrigo, and A. Alvarez-Larran
Blood cell activation in myeloproliferative neoplasms
Haematologica, November 1, 2009; 94(11): 1484 - 1488.
[Full Text] [PDF]