Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1993-06-18
1999-07-20
Teng, Sally P.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
530350, 4352523, 43525411, 435325, 435348, 435352, 435365, 4353201, C12N 1512, C07K 14705
Patent
active
059257504
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Myeloproliferative diseases are diseases in which hematopoietic stem cells exhibit an impairment in their differentiation capacity and/or an impairment of their dependence on a specific growth factor.
Blood cells derive from a small number of stem cells capable of self-nenewal which generate progenitor cells irreversibly committed to the production of one or a few hematopoietic lines. Precise control of each step of differentiation is necessary in order to ensure a stable level of the different specialized cells as well as to provide a precise response to stimulations caused by stress. The controls are usually due to the effect of interactions between cells, either resulting from contact with the hematopoietic micro-environment or from the release of specific cytokines. The breakdown of the control systems leads either to cytopenias or to an uncontrolled cellular proliferation which may affect one or more lines depending on the nature of the lesion. The proliferation of several hematopoietic lines may lead to a myeloproliferative disease. Such diseases can be induced by retroviruses carrying oncogenes such as the retrovirus MPLV, an abbreviation for "myeloproliferative leukemia virus" which is a retrovirus defective with respect to its replication.
It is known that the murine retrovirus MPLV causes a severe hematological disorder in adult mice of most strains, characterized by a dramatic proliferation and a differentiation of several hematopoietic lines. The most acute aspect of this disease is the suppression of the in vitro dependence on growth factors for most of the hematopoietic progenitor cells. The natural MPLV isolate has been described as being a complex of two viral entities: a murine virus F-MuLV (Friend replication competent ecotropic murine leukemia virus) and a virus defective with respect to its replication now designated by the term MPLV. The pseudotyping of the defective particles with other ecotropic or amphotropic MuLV viruses enables the initial disease to be reproduced. It has been shown that the proviral DNA of MPLV and the DNA of F-MuLV are structurally similar except in the envelope region.
The inventors have now identified a sequence of cellular origin transduced in the rearranged gene of the MPLV envelope and which proves to be conserved in the mammalian genome.
The identification of this sequence has enabled its importance in phenomena which have similarities with a myeloproliferative disease to be demonstrated.
The invention thus relates to a polypeptide capable of playing a role when it is produced by a virus of the MPLV type in the disturbances caused during myeloproliferative diseases. The invention also relates to nucleotide sequences coding for this polypeptide.
The inventors have made the very interesting observation that the protein sequence of the polypeptide of the invention exhibits pronounced analogies with certain amino acid sequences of growth factor receptors. Consequently, the invention makes possible the identification of the mechanisms of the disease linked to the infection by the retrovirus MPLV and suggests agents for the detection of a disease of the same type in man and optionally, for its treatment.
DESCRIPTION OF THE FIGURES
FIGS. 1A and B: (A) Restriction map of the clone MPLV 107 and clone F-MuLV 57 obtained by digestion with restriction endonucleases. The restriction sites for the following enzymes are designated as follows: B: BamHI, C:ClaI, E:EcoRI, H:HindIII, K:KpnI, P:PstI, Pv:PvuII, SI:SacI, SII:SacII, X:XbaI. The thick black line corresponds to the region specific to MPLV. The two probes derived from the MPLV envelope gene are shown by the thick black lines below the restriction map.
(B) Demonstration of the specificity of the probes derived from the MPLV envelope by northern analysis. Poly A.sup.+ RNA was obtained from NIH 3T3 cells infected with the amphotropic 4070 pseudotype of MPLV (5 .mu.g, lanes A) or with the clone F-MuLV 57 (1 .mu.g, lanes B), and the non-producing Mus dunni clone 2 infected with MPLV (15 .
REFERENCES:
patent: 5580753 (1996-12-01), Yang et al.
Penciolelli et al., "Genetic Analysis of Myeloproliferative Leukemia Virus, Novel Acute Leukemogenic Replication-Defective Retrovirus", J. Virology, 61:579-583 (1987).
Vigon et al., Oncogene, 8, 2607, 1993.
Wallace et al., Methods in Enzymology, 152, 432, 1987.
Bartley, R. T. et al., 1994, "Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl," Cell 77: 1117-1124.
Benit, L. et al., 1994, "Characterization of mpl cytoplasmic domain sequences required for myeloproliferative leukemia virus pathogenicity," J. Virology 68:5270-5274.
Courtois, G. et al., 1995, "Constitutive activation of a variant of the env-mpl oncogene product by disulfide-linked homodimerization," J. Virology 69:2794-2800.
de Sauvage, F. et al., 1994, "Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand," Nature 369:533-538.
Le Coniat, M. et al., 1989, "The human homolog of the myeloproliferative virus maps to chromosome band 1p34," Hum. Genetics 83:194-196.
Methia, N. et al., 1993, "Oligodeoxynucleotides antisense to the proto-oncogene c-mpl specifically inhibit in vitro megakaryocytopoiesis," Blood 82:1395-1401.
Wendling, F. et al., 1994, "c-Mpl ligand is a humoral regulator of megakaryocytopoiesis," Nature 369:571-574.
Wendling, F. et al., 1990, "Myeloproliferative leukemia virus sustains proliferation and differentiation of hematopoietic progenitor cells," Exp. Hematol. 18:624.
Wendling, F. et al., 1989, "Myeloid progenitor cells transformed by the myeloproliferative leukemia virus proliferate and differentiate in vitro without the addition of growth factors," Leukemia 3:475-480.
Wendling, F. et al., 1989, "Factor-independent erythropoietic progenitor cells in leukemia induced by the myeloproliferative leukemia virus," Blood 73:1161-1167.
Wendling, F et al., 1986, "MPLV: a retrovirus complex inducing an acute myeloroliferative leukemic disorder in adult mice," Virology 149:242-246.
Benit et al., Oncogene, 8, 787, 1993.
Souyri et al., Cell, 63, 1137, 1990.
Vigon et al., PNAS, 89, 5640, 1992.
Skoda et al., EMBO, 12, 2645, 1993.
Charon Martine
Gisselbrecht Sylvie
Penciolelli Jean-Francios
Souyri Michele
Tambourin Pierre
Institute National de la Sante et de la Recherche Medicale (INSE
Teng Sally P.
LandOfFree
Nucleic acid encoding polypeptide of a growth factor receptor fa does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nucleic acid encoding polypeptide of a growth factor receptor fa, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleic acid encoding polypeptide of a growth factor receptor fa will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1322867