Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia

Yoko Horikawa, Itaru Matsumura, Koji Hashimoto, Masamichi Shiraga, Satoru Kosugi, Seiji Tadokoro, Takashi Kato, Hiroshi Miyazaki, Yoshiaki Tomiyama, Yoshiyuki Kurata, Yuji Matsuzawa, Yuzuru Kanakura*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

168 Citations (Scopus)

Abstract

Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis through binding to the cytokine receptor c-Mpl (the product of the c-mpl proto-oncogene). In an effort to determine the pathophysiological role of TPO-c-Mpl system in essential thrombocythemia (ET), we have examined the levels of serum TPO and the expression and function of platelet c-Mpl in 17 patients with ET. In spite of extreme thrombocytosis, serum TPO levels were slightly elevated or within normal range in most, if not all, patients with ET (mean ± SD, 1.31 ± 1.64 fmol mL), as compared with normal subjects (0.76 ± 0.21 fmol/mL). Flow cytometric and Western blot analyses revealed that the expression of platelet c-Mpl was strikingly reduced in all patients with ET. Furthermore, the expression of platelet c-mpl mRNA was found to be significantly decreased in the ET patients tested. In contrast, almost identical levels of GPIIb/IIIa protein and mRNA were expressed in platelets from ET patients and normal controls. In addition to expression level, activation state of platelet c-Mpl was investigated in ET patients. Immunoblotting with anti-phosphotyrosine antibody showed that no aberrant protein-tyrosine phosphorylation was observed in platelets of ET patients before treatment with TPO, and the levels of TP-induced protein-tyrosine phosphorylation, including c-Mpl- tyrosyl phosphorylation, roughly paralleled those of c-Mpl expression, suggesting that c-Mpl-mediated signaling pathway was not constitutively activated in platelets of ET patients. These results suggested that the TPO- c-Mpl system may not be directly linked to pathogenesis of ET, and that gene(s) mutated in ET may be important in regulating the levels of c-mpl gene expression in addition to the growth and differentiation of multipotential hematopoietic stem cells.

Original languageEnglish
Pages (from-to)4031-4038
Number of pages8
JournalBlood
Volume90
Issue number10
DOIs
Publication statusPublished - 1997 Nov 15
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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