title: Study of the thrombopoitin receptor in essential thrombocythemia.
abstract: Essential thrombocythemia (ET) is a myeloproliferative disorder associated with megakaryocytic hyperplasia and thrombocytosis. In this disease, in vitro autonomous growth of megakaryocytic colonies has been demonstrated by various investigators. This phenomenon is impaired by the inhibition of the thrombopoietin/c-mpl pathway. In order to evaluate the potential role of mutations of the receptor gene in the origin of this autonomous growth, we compared the expression of c-mpl mRNA isoforms in platelets derived from ET patients and normal subjects. Overlapping c-mpl PCR fragments derived from four ET patients were sequenced to search for small mutations. In the 10 ET and five normal samples we studied, relative expression of the c-mpl isoforms was identical. New variants of Mpl-P and K isoforms, Mpl-P2 and K2 were detected. Cloning of these isoforms indicated that they are produced by alternative splicing of exon 9 sequences shared by Mpl-P and K. Their predicted amino acid sequence would be deleted by 24 aminoacids, upstream of the WSSWS box of the second domain of c-mpl. Two sequence variations, leading to DNA restriction polymorphisms, were present in the extracellular and Mpl-K intracytoplasmic domains. Both were present in normal and ET samples, excluding mutations of c-mpl as a cause of ET.
authors.affiliation: Unité INSERM U 409, Faculté de Médecine X Bichat, Paris, France.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kiladjian
authors.forename: N
authors.initials: N
authors.lastname: Elkassar
authors.forename: G
authors.initials: G
authors.lastname: Hetet
authors.forename: J
authors.initials: J
authors.lastname: Briere
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
authors.forename: C
authors.initials: C
authors.lastname: Gardin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001792:Blood Platelets / Q000378:metabolism*; D017931:DNA Primers; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D017422:Sequence Analysis, DNA; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human