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Blood, 4 June 2009, Vol. 113, No. 23, pp. 5942-5950. Prepublished online as a Blood First Edition Paper on February 4, 2009; DOI 10.1182/blood-2008-09-179416. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-09-179416v1 113/23/5942    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Ishii, T. Articles by Xu, M. PubMed PubMed Citation Articles by Ishii, T. Articles by Xu, M. Related Collections Myeloid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Pivotal role of mast cells in pruritogenesis in patients with myeloproliferative disorders Takefumi Ishii1,*, Jiapeng Wang1,*, Wei Zhang1, John Mascarenhas1, Ronald Hoffman1,2, Ying Dai1, Nathaniel Wisch1, and Mingjiang Xu1,2 1 Division of Hematology/Oncology, Tisch Cancer Institute and Department of Medicine, Mount Sinai School of Medicine, New York, NY; and 2 Myeloproliferative Disorders Research Consortium, New York, NY Pruritus is a common symptom in patients with Philadelphia chromosome–negative myeloproliferative disorders (MPDs). The pathophysiology of MPD-associated pruritus is unclear. We have demonstrated that MPD mast cells (MCs) are involved by the malignant process. In the present study, we explored the hypothesis that MCs play an important role in the development of pruritogenesis in MPDs. We found that MPD MCs released significantly greater amounts of pruritogenic factors, including histamine, leukotrienes, and interleukin-31 (IL-31) than normal MCs. Elevated levels of IL-31 were also observed in MPD CD3+ cell-conditioned media. MPD MCs exhibited increased migratory behavior in response to stem cell factor or interleukin-8, which was associated with increased filamentous-actin content. Furthermore, the presence of pruritus in MPDs was statistically correlated with a greater number of MCs being generated by CD34+ cells, a greater number of MC colonies being formed by CD34+ cells, decreased apoptosis and prostaglandin D2 release by cultured MCs, and higher plasma levels of IL-31. These data demonstrate that functional abnormalities of MPD MCs probably lead to pruritogenesis in patients with MPDs. These studies provide cellular and molecular targets for the development of antipruritus drugs for patients with MPDs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Itchy mast cells in MPNs Ruben A. Mesa Blood 2009 113: 5697-5698. [Full Text] [PDF] This article has been cited by other articles: 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] L. Pieri, C. Bogani, P. Guglielmelli, M. Zingariello, R. A. Rana, N. Bartalucci, A. Bosi, and A. M. Vannucchi The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera Haematologica, November 1, 2009; 94(11): 1537 - 1545. [Abstract] [Full Text] [PDF] Pruritus in Myeloproliferative Disorders Journal Watch Oncology and Hematology, July 21, 2009; 2009(721): 1 - 1. [Full Text] R. A. Mesa Itchy mast cells in MPNs Blood, June 4, 2009; 113(23): 5697 - 5698. [Full Text] [PDF]

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