|
|
 Previous Article | Table of Contents | Next Article 
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, and
Yuzuru Kanakura
From the Departments of Internal Medicine II, Hematology and Oncology, and Blood Transfusion, Osaka University Medical School, Osaka, Japan; and Pharmaceutical Research Laboratory, Kirin Brewery Co Ltd, Gunma, Japan.
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 TPO-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.
Blood, Vol. 90 No. 10 (November 15), 1997:
pp. 4031-4038
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Tiedt, J. Coers, S. Ziegler, A. Wiestner, H. Hao-Shen, C. Bornmann, J. Schenkel, S. Karakhanova, F. J. de Sauvage, C. W. Jackson, et al.
Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes
Blood,
February 19, 2009;
113(8):
1768 - 1777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Senyuk, C. R. Rinaldi, D. Li, F. Cattaneo, A. Stojanovic, F. Pane, X. Du, N. Mahmud, J. Dickstein, and G. Nucifora
Consistent Up-regulation of Stat3 Independently of Jak2 Mutations in a New Murine Model of Essential Thrombocythemia
Cancer Res.,
January 1, 2009;
69(1):
262 - 271.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Tiedt, H. Hao-Shen, M. A. Sobas, R. Looser, S. Dirnhofer, J. Schwaller, and R. C. Skoda
Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice
Blood,
April 15, 2008;
111(8):
3931 - 3940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Moliterno, D. M. Williams, O. Rogers, and J. L. Spivak
Molecular mimicry in the chronic myeloproliferative disorders: reciprocity between quantitative JAK2 V617F and Mpl expression
Blood,
December 1, 2006;
108(12):
3913 - 3915.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Pang, H.-H. Xue, G. Szalai, X. Wang, Y. Wang, D. K. Watson, W. J. Leonard, G. A. Blobel, and M. Poncz
Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins
Blood,
October 1, 2006;
108(7):
2198 - 2206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bellanne-Chantelot, I. Chaumarel, M. Labopin, F. Bellanger, V. Barbu, C. De Toma, F. Delhommeau, N. Casadevall, W. Vainchenker, G. Thomas, et al.
Genetic and clinical implications of the Val617Phe JAK2 mutation in 72 families with myeloproliferative disorders
Blood,
July 1, 2006;
108(1):
346 - 352.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Schafer
Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia
Blood,
June 1, 2006;
107(11):
4214 - 4222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tefferi
Pathogenesis of Myelofibrosis With Myeloid Metaplasia
J. Clin. Oncol.,
November 20, 2005;
23(33):
8520 - 8530.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Heller, A. C. Glembotsky, M. J. Gandhi, C. L. Cummings, C. J. Pirola, R. F. Marta, L. I. Kornblihtt, J. G. Drachman, and F. C. Molinas
Low Mpl receptor expression in a pedigree with familial platelet disorder with predisposition to acute myelogenous leukemia and a novel AML1 mutation
Blood,
June 15, 2005;
105(12):
4664 - 4670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kralovics, F. Passamonti, A. S. Buser, S.-S. Teo, R. Tiedt, J. R. Passweg, A. Tichelli, M. Cazzola, and R. C. Skoda
A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
N. Engl. J. Med.,
April 28, 2005;
352(17):
1779 - 1790.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ding, H. Komatsu, A. Wakita, M. Kato-Uranishi, M. Ito, A. Satoh, K. Tsuboi, M. Nitta, H. Miyazaki, S. Iida, et al.
Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin
Blood,
June 1, 2004;
103(11):
4198 - 4200.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Schafer
Thrombocytosis
N. Engl. J. Med.,
March 18, 2004;
350(12):
1211 - 1219.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kralovics, A. S. Buser, S.-S. Teo, J. Coers, A. Tichelli, A. P. C. van der Maas, and R. C. Skoda
Comparison of molecular markers in a cohort of patients with chronic myeloproliferative disorders
Blood,
September 1, 2003;
102(5):
1869 - 1871.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tefferi
Polycythemia Vera: A Comprehensive Review and Clinical Recommendations
Mayo Clin. Proc.,
February 1, 2003;
78(2):
174 - 194.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. L. Spivak
Polycythemia vera: myths, mechanisms, and management
Blood,
December 15, 2002;
100(13):
4272 - 4290.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Teofili, F. Pierconti, A. Di Febo, N. Maggiano, N. Vianelli, S. Ascani, E. Rossi, S. Pileri, G. Leone, L. M. Larocca, et al.
The expression pattern of c-mpl in megakaryocytes correlates with thrombotic risk in essential thrombocythemia
Blood,
June 28, 2002;
100(2):
714 - 717.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Mesa, C. A. Hanson, C.-Y. Li, S.-Y. Yoon, S. V. Rajkumar, G. Schroeder, and A. Tefferi
Diagnostic and prognostic value of bone marrow angiogenesis and megakaryocyte c-Mpl expression in essential thrombocythemia
Blood,
May 13, 2002;
99(11):
4131 - 4137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Axelrad, D. Eskinazi, P. N. Correa, and D. Amato
Hypersensitivity of circulating progenitor cells to megakaryocyte growth and development factor (PEG-rHu MGDF) in essential thrombocythemia
Blood,
November 15, 2000;
96(10):
3310 - 3321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tefferi, S.-Y. Yoon, and C.-Y. Li
Immunohistochemical staining for megakaryocyte c-mpl may complement morphologic distinction between polycythemia vera and secondary erythrocytosis
Blood,
July 15, 2000;
96(2):
771 - 772.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Letestu, N. Vitrat, A. Masse, J.-P. L. Couedic, V. Lazar, P. Rameau, F. Wendling, J. Vuillier, P. Boutard, E. Plouvier, et al.
Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome
Blood,
March 1, 2000;
95(5):
1633 - 1641.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Tanaka, I. Matsumura, K. Nakajima, H. Daino, J. Sonoyama, H. Yoshida, K. Oritani, T. Machii, M. Yamamoto, T. Hirano, et al.
GATA-1 blocks IL-6-induced macrophage differentiation and apoptosis through the sustained expression of cyclin D1 and Bcl-2 in a murine myeloid cell line M1
Blood,
February 15, 2000;
95(4):
1264 - 1273.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Moliterno and J. L. Spivak
Posttranslational Processing of the Thrombopoietin Receptor Is Impaired in Polycythemia Vera
Blood,
October 15, 1999;
94(8):
2555 - 2561.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Taksin, J.-P. L. Couedic, I. Dusanter-Fourt, A. Masse, S. Giraudier, A. Katz, F. Wendling, W. Vainchenker, N. Casadevall, and N. Debili
Autonomous Megakaryocyte Growth in Essential Thrombocythemia and Idiopathic Myelofibrosis Is Not Related to a c-mpl Mutation or to an Autocrine Stimulation by Mpl-L
Blood,
January 1, 1999;
93(1):
125 - 139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kondo, M. Okabe, M. Sanada, M. Kurosawa, S. Suzuki, M. Kobayashi, M. Hosokawa, and M. Asaka
Familial Essential Thrombocythemia Associated With One-Base Deletion in the 5'-Untranslated Region of the Thrombopoietin Gene
Blood,
August 15, 1998;
92(4):
1091 - 1096.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Schwartz
Polycythemia Vera -- Chance, Death, and Mutability
N. Engl. J. Med.,
February 26, 1998;
338(9):
613 - 615.
[Full Text]
|
|
|
|
|
