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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4198-4200. Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-10-3471. This Article Full Text (PDF) Supplemental Table All Versions of this Article: 2003-10-3471v1 103/11/4198    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles via Google Scholar Google Scholar Articles by Ding, J. Articles by Ueda, R. Search for Related Content PubMed PubMed Citation Articles by Ding, J. Articles by Ueda, R. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted October 10, 2003 Accepted January 20, 2004 Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin Jianmin Ding, Hirokazu Komatsu*, Atsushi Wakita, Miyuki Kato-Uranishi, Masato Ito, Atsushi Satoh, Kazuya Tsuboi, Masakazu Nitta, Hiroshi Miyazaki, Shinsuke Iida, and Ryuzo Ueda Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Science, Nagoya, Aichi, Japan Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi-gun, Aichi, Japan Kirin Brewery Company, Ltd., Tokyo, Japan * Corresponding author; email: komatsu{at}med.nagoya-cu.ac.jp. One Japanese pedigree of familial essential thrombocythemia (FET) inherited as an autosomal-dominant manner is presented. A unique point mutation, serine505asparagine505 (Ser505Asn505), was identified in the transmembrane domain of the c-MPL gene in all of the eight members with thrombocythemia, but in none of the other eight unaffected members in this FET family. The Ba/F3 cells expressing the mutant Asn505 acquired interleukin-3 (IL-3)-independent survival capacity, while those expressing wild-type Ser505 did not. The autonomous phosphorylation of Mek1/2 and Stat5b was observed in the mutant Ba/F3 cells in the absence of IL-3. The former was also found in platelets derived from the affected individual in the absence of thrombopoietin. These results show that the Asn505 is an activating mutation with respect to the intracellular signaling and survival of the cells. This is the first report of FET, deriving from a dominant-positive activating mutation of the c-MPL gene. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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