|
|
 Previous Article | Table of Contents | Next Article 
Oligodeoxynucleotides antisense to the proto-oncogene c-mpl specifically
inhibit in vitro megakaryocytopoiesis
N Methia, F Louache, W Vainchenker and F Wendling
INSERM U 362, Institut Gustave Roussy, Villejuif, France.
The proto-oncogene c-mpl encodes a protein whose sequence shares striking
homologies with members of the highly conserved hematopoietin receptor
superfamily. This gene had been transduced in a truncated form by the acute
leukemogenic murine Myeloproliferative leukemia virus, which exhibits the
unique property of inducing factor-independent proliferation and terminal
differentiation of a broad spectrum of hematopoietic progenitors.
Presently, the ligand and the role of c-mpl in the regulation of normal
hematopoiesis are unknown. To show the function of c-mpl, its expression
was first examined in human purified hematopoietic cell populations and,
then, an antisense strategy was used. By RNA-based polymerase chain
reaction, c-mpl transcripts were detected in purified CD34+ cells,
megakaryocytes, and platelets. Synthetic unmodified antisense
oligodeoxynucleotides were derived from different regions of the c-mpl
extracellular domain. On in vitro exposure of CD34+ cells, two antisense
oligomers led to a 50% to 70% inhibition of c-mpl mRNA synthesis, whereas
their respective sense had no effect. Furthermore, the decrease in c-mpl
mRNA correlated with a significant inhibition (range, 54% to 81%) of in
vitro megakaryocytic colony formation (CFU-MK), whereas the growth of
erythroid (BFU-E) or granulomacrophage (CFU-GM) colonies was unaffected.
The data provide first evidences that c-mpl is involved in
megakaryocytopoiesis. In addition, the results raise the possibility that
this proto-oncogene encodes the receptor for a new cytokine specifically
regulating thrombocytopoiesis.
Volume 82,
Issue 5,
pp. 1395-1401,
09/01/1993
Copyright © 1993 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:
|
|
|
|
 
K. Kaushansky
Historical review: megakaryopoiesis and thrombopoiesis
Blood,
February 1, 2008;
111(3):
981 - 986.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Chaligne, C. James, C. Tonetti, R. Besancenot, J. P. Le Couedic, F. Fava, F. Mazurier, I. Godin, K. Maloum, F. Larbret, et al.
Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis
Blood,
November 15, 2007;
110(10):
3735 - 3743.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Srivastava, E. Nedelcu, B. Esmaeli-Azad, R. Mishra, and E. Carrier
Thrombopoietin Enhances Generation of CD34+ Cells from Human Embryonic Stem Cells
Stem Cells,
June 1, 2007;
25(6):
1456 - 1461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Lupia, O. Bosco, S. Bergerone, A. E. Dondi, A. Goffi, E. Oliaro, M. Cordero, L. Del Sorbo, G. Trevi, and G. Montrucchio
Thrombopoietin Contributes to Enhanced Platelet Activation in Patients With Unstable Angina
J. Am. Coll. Cardiol.,
December 5, 2006;
48(11):
2195 - 2203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Corazza, C. Hermans, S. D'Hondt, A. Ferster, A. Kentos, Y. Benoit, and E. Sariban
Circulating thrombopoietin as an in vivo growth factor for blast cells in acute myeloid leukemia
Blood,
March 15, 2006;
107(6):
2525 - 2530.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. C.R. Perlingeiro, M. Kyba, S. Bodie, and G. Q. Daley
A Role for Thrombopoietin in Hemangioblast Development
Stem Cells,
May 1, 2003;
21(3):
272 - 280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Xie, R. J. Chan, S. A. Johnson, M. Starr, J. McCarthy, R. Kapur, and M. C. Yoder
Thrombopoietin promotes mixed lineage and megakaryocytic colony-forming cell growth but inhibits primitive and definitive erythropoiesis in cells isolated from early murine yolk sacs
Blood,
February 15, 2003;
101(4):
1329 - 1335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Kuter and C. G. Begley
Recombinant human thrombopoietin: basic biology and evaluation of clinical studies
Blood,
November 15, 2002;
100(10):
3457 - 3469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. C. Haznedaroglu, H. Goker, M. Turgut, Y. Buyukasik, and M. Benekli
Thrombopoietin as a Drug: Biologic Expectations, Clinical Realities, and Future Directions
Clinical and Applied Thrombosis/Hemostasis,
July 1, 2002;
8(3):
193 - 212.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. M. Gewirtz
Oligonucleotide Therapeutics: A Step Forward
J. Clin. Oncol.,
May 9, 2000;
18(9):
1809 - 1811.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-M. Luoh, E. Stefanich, G. Solar, H. Steinmetz, T. Lipari, T. I. Pestina, C. W. Jackson, and F. J. de Sauvage
Role of the Distal Half of the c-Mpl Intracellular Domain in Control of Platelet Production by Thrombopoietin In Vivo
Mol. Cell. Biol.,
January 15, 2000;
20(2):
507 - 515.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
N. Sawai, K. Koike, H. H. Mwamtemi, T. Kinoshita, Y. Kurokawa, K. Sakashita, T. Higuchi, K. Takeuchi, M. Shiohara, T. Kamijo, et al.
Thrombopoietin Augments Stem Cell Factor-Dependent Growth of Human Mast Cells From Bone Marrow Multipotential Hematopoietic Progenitors
Blood,
June 1, 1999;
93(11):
3703 - 3712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-A. Hunnestad, R. Steen, G. E. Tjønnfjord, and T. Egeland
Thrombopoietin Combined with Early-Acting Growth Factors Effectively Expands Human Hematopoietic Progenitor Cells In Vitro
Stem Cells,
January 1, 1999;
17(1):
31 - 38.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
N. Sawai, K. Koike, S. Ito, Y. Kurokawa, H. H. Mwamtemi, T. Kinoshita, K. Sakashita, T. Higuchi, K. Takeuchi, M. Shiohara, et al.
Apoptosis of Erythroid Precursors under Stimulation with Thrombopoietin: Contribution to Megakaryocytic Lineage Choice
Stem Cells,
January 1, 1999;
17(1):
45 - 54.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. Wagemaker, K. J. Neelis, S. C.C. Hartong, A. W. Wognum, G. R. Thomas, P. J. Fielder, and D. L. Eaton
The Efficacy of Recombinant Thrombopoietin in Murine and Nonhuman Primate Models for Radiation-Induced Myelosuppression and Stem Cell Transplantation
Stem Cells,
November 1, 1998;
16(6):
375 - 386.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. Komura, T. Matsumura, T. Kato, T. Tahara, Y. Tsunoda, and T. Sawada
Thrombopoietin in Patients with Hepatoblastoma
Stem Cells,
September 1, 1998;
16(5):
329 - 333.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. Matsunaga, T. Kato, H. Miyazaki, and M. Ogawa
Thrombopoietin Promotes the Survival of Murine Hematopoietic Long-Term Reconstituting Cells: Comparison With the Effects of FLT3/FLK-2 Ligand and Interleukin-6
Blood,
July 15, 1998;
92(2):
452 - 461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. P. Hammond, T. Wun, A. Kaplan, S. Kaplan, T. Paglieroni, K. Kaushansky, and D. C. Foster
High Concentrations of Thrombopoietin Activate Platelets In Vitro
Clinical and Applied Thrombosis/Hemostasis,
July 1, 1998;
4(3):
170 - 178.
[Abstract]
[PDF]
|
|
|
|
|
|
|
G. P. Solar, W. G. Kerr, F. C. Zeigler, D. Hess, C. Donahue, F. J. de Sauvage, and D. L. Eaton
Role of c-mpl in Early Hematopoiesis
Blood,
July 1, 1998;
92(1):
4 - 10.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Sawai, K. Koike, T. Higuchi, K. Ogami, and M. Oda
Thrombopoietin Enhances the Production of Myeloid Cells, but not Megakaryocytes, in Juvenile Chronic Myelogenous Leukemia
Blood,
June 1, 1998;
91(11):
4065 - 4073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Williams, G. G. Pipia, N. S. Datta, and M. W. Long
Thrombopoietin Requires Additional Megakaryocyte-Active Cytokines for Optimal Ex Vivo Expansion of Megakaryocyte Precursor Cells
Blood,
June 1, 1998;
91(11):
4118 - 4126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Bruno, S. K. Horrigan, D. Van Den Berg, E. Rozler, P. R. Fitting, S. T. Moss, C. Westbrook, and R. Hoffman
The Smad5 Gene Is Involved in the Intracellular Signaling Pathways That Mediate the Inhibitory Effects of Transforming Growth Factor-beta on Human Hematopoiesis
Blood,
March 15, 1998;
91(6):
1917 - 1923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Cardier and J. Dempsey
Thrombopoietin and Its Receptor, c-mpl, Are Constitutively Expressed by Mouse Liver Endothelial Cells: Evidence of Thrombopoietin as a Growth Factor for Liver Endothelial Cells
Blood,
February 1, 1998;
91(3):
923 - 929.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. C. Daw, J. T. Arnold, B. A. Abushullaih, P. E. Stenberg, M. M. White, D. Jayawardene, D. Kumar Srivastava, and C. W. Jackson
A Single Intravenous Dose of Murine Megakaryocyte Growth and Development Factor Potently Stimulates Platelet Production, Challenging the Necessity for Daily Administration
Blood,
January 15, 1998;
91(2):
466 - 474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ishida, T. Ito, and S.-i. Kuriya
Effects of C-Mpl Ligand on Cytoplasmic Maturation of Murine Megakaryocytes and on Platelet Production
J. Histochem. Cytochem.,
January 1, 1998;
46(1):
49 - 58.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Murone, D. A. Carpenter, and F. J. de Sauvage
Hematopoietic Deficiencies in c-mpl and TPO Knockout Mice
Stem Cells,
January 1, 1998;
16(1):
1 - 6.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
N. S. Weich, A. Wang, M. Fitzgerald, T. Y. Neben, D. Donaldson, J. Giannotti, J. Yetz-Aldape, R. M. Leven, and K. J. Turner
Recombinant Human Interleukin-11 Directly Promotes Megakaryocytopoiesis In Vitro
Blood,
November 15, 1997;
90(10):
3893 - 3902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Horikawa, I. Matsumura, K. Hashimoto, M. Shiraga, S. Kosugi, S. Tadokoro, T. Kato, H. Miyazaki, Y. Tomiyama, Y. Kurata, et al.
Markedly Reduced Expression of Platelet c-mpl Receptor in Essential Thrombocythemia
Blood,
November 15, 1997;
90(10):
4031 - 4038.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Wakikawa, A. Shioi, M. Hino, M. Inaba, Y. Nishizawa, N. Tatsumi, H. Morii, and S. Otani
Thrombopoietin Inhibits in Vitro Osteoclastogenesis from Murine Bone Marrow Cells
Endocrinology,
October 1, 1997;
138(10):
4160 - 4166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Abraham and R. L. Basser
Megakaryocyte Growth and Development Factor: A Review of Early Clinical Studies
Oncologist,
October 1, 1997;
2(5):
311 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Neelis, S. C.C. Hartong, T. Egeland, G. R. Thomas, D. L. Eaton, and G. Wagemaker
The Efficacy of Single-Dose Administration of Thrombopoietin With Coadministration of Either Granulocyte/Macrophage or Granulocyte Colony-Stimulating Factor in Myelosuppressed Rhesus Monkeys
Blood,
October 1, 1997;
90(7):
2565 - 2573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. J. Borge, V. Ramsfjell, L. Cui, and S. E.W. Jacobsen
Ability of Early Acting Cytokines to Directly Promote Survival and Suppress Apoptosis of Human Primitive CD34+CD38- Bone Marrow Cells With Multilineage Potential at the Single-Cell Level: Key Role of Thrombopoietin
Blood,
September 15, 1997;
90(6):
2282 - 2292.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Neelis, L. Qingliang, G. R. Thomas, B. L. Cohen, D. L. Eaton, and G. Wagemaker
Prevention of Thrombocytopenia by Thrombopoietin in Myelosuppressed Rhesus Monkeys Accompanied by Prominent Erythropoietic Stimulation and Iron Depletion
Blood,
July 1, 1997;
90(1):
58 - 63.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Goncalves, C. Lacout, J.-L. Villeval, F. Wendling, W. Vainchenker, and D. Dumenil
Thrombopoietin Does Not Induce Lineage-Restricted Commitment of Mpl-R Expressing Pluripotent Progenitors But Permits Their Complete Erythroid and Megakaryocytic Differentiation
Blood,
May 15, 1997;
89(10):
3544 - 3553.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. C. Broudy, N. L. Lin, D. F. Sabath, T. Papayannopoulou, and K. Kaushansky
Human Platelets Display High-Affinity Receptors for Thrombopoietin
Blood,
March 15, 1997;
89(6):
1896 - 1904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Era, T. Takahashi, K. Sakai, K. Kawamura, and T. Nakano
Thrombopoietin Enhances Proliferation and Differentiation of Murine Yolk Sac Erythroid Progenitors
Blood,
February 15, 1997;
89(4):
1207 - 1213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Levin
Thrombopoietin -- Clinically Realized?
N. Engl. J. Med.,
February 6, 1997;
336(6):
434 - 436.
[Full Text]
|
|
|
|
|
|
|
T. J. Gonda and R. J. D'Andrea
Activating Mutations in Cytokine Receptors: Implications for Receptor Function and Role in Disease
Blood,
January 15, 1997;
89(2):
355 - 369.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Birkmann, S. Oez, M. Smetak, G. Kaiser, H. Kappauf, and W. M. Gallmeier
Effects of Recombinant Human Thrombopoietin Alone and in Combination with Erythropoietin and Early-Acting Cytokines on Human Mobilized Purified CD34+ Progenitor Cells Cultured in Serum-Depleted Medium
Stem Cells,
January 1, 1997;
15(1):
18 - 32.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. E.J. Rasko, E. O'Flaherty, and C. G. Begley
Mpl Ligand (MGDF) Alone and in Combination with Stem Cell Factor (SCF) Promotes Proliferation and Survival of Human Megakaryocyte, Erythroid and Granulocyte/Macrophage Progenitors
Stem Cells,
January 1, 1997;
15(1):
33 - 42.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. Andrews, A Winkler, D Myerson, R. Briddell, G. Knitter, I. McNiece, and P Hunt
Recombinant human ligand for MPL, megakaryocyte growth and development factor (MGDF), stimulates thrombopoiesis in vivo in normal and myelosuppressed baboons
Stem Cells,
November 1, 1996;
14(6):
661 - 677.
[Abstract]
|
|
|
|
|
|
|
M Schattner, P Lefebvre, S. Mingolelli, C. Goolsby, A Rademaker, J. White, D Foster, D Green, and I Cohen
Thrombopoietin-stimulated ex vivo expansion of human bone marrow megakaryocytes
Stem Cells,
March 1, 1996;
14(2):
207 - 214.
[Abstract]
|
|
|
|
|
|
|
D. J. Kuter
Thrombopoietin: Biology and Clinical Applications
Oncologist,
February 1, 1996;
1(1):
98 - 106.
[Abstract]
[Full Text]
[PDF]
|
|
| |
