title: Clonal analysis of haemopoietic cells in essential thrombocythaemia.
abstract: Essential thrombocythaemia (ET) is a myeloproliferative disease (MPD) predominantly involving the platelet lineage, with a diagnosis often difficult to establish in practice. The demonstration of a clonal haemopoiesis can contribute to diagnosis. The clonal origin of blood cells can be assessed in female patients using X-chromosome-linked polymorphisms, assuming a random inactivation of the X chromosome. The human androgen receptor gene HUMARA has been used for this purpose, taking advantage of a highly polymorphic trinucleotide repeat in the first exon. The close proximity of the polymorphic trinucleotide repeat to four methylation sites permits a clonal analysis based on the polymerase chain reaction. We have used this technique to study the clonality of haemopoietic cells in 32 patients with ET and 23 age-matched control heterozygotes for the HUMARA polymorphism. A monoclonal pattern of haemopoiesis was detected in unfractionated nucleated blood cells from 22 patients, suggesting that haemopoiesis is essentially monoclonal in a majority of cases in this disease. In some patients a monoclonality of granulocytes was documented, whereas the mononuclear fraction had a polyclonal pattern of X-inactivation. Finally, in two patients for whom a polyclonality had been found in unfractionated blood, analysis of G6PD transcripts in platelets revealed a clonal megakaryocytopoiesis. These findings confirm the heterogeneity of haematological abnormalities in ET patients and the potential utility of a multifaceted laboratory approach to investigate these patients.
authors.affiliation: INSERM U409, Faculté de Médecine X, Bichat, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: el Kassar
authors.forename: G
authors.initials: G
authors.lastname: Hetet
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Brière
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D003114:Colony-Forming Units Assay; D004303:Dosage Compensation, Genetic; D005260:Female; D005500:Follow-Up Studies; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000097:blood*
chemical_list: D011944:Receptors, Androgen; D005954:Glucosephosphate Dehydrogenase