title: Blastic transformation in essential thrombocythemia. In vitro differentiation of blast cells into granulocytic, erythroid, and megakaryocytic lineages.
abstract: A 57-year-old man with essential thrombocythemia (ET) developed myelofibrosis, that progressed to a blastic transformation state. The characteristics of the blastic cells were serially studied both morphologically and phenotypically as well as in cell culture. The blastic cells that were first detected in peripheral blood had features of myeloid stem cells with slight differentiation toward megakaryocytic lineage. However, later in the course, most of the blastic cells were immature. During culture in the presence of human plasma-derived serum (PDS), some blastic cells obtained at the initial stage differentiated, mainly to both granulocytes and macrophages morphologically, but later tended to differentiate into both megakaryocytes and macrophages. Finally the blasts appeared to have lost their ability to differentiate morphologically. However, the blasts formed mixed colonies consisting of erythroblasts, granulocytes, macrophages, and immature blasts when cultured in methylcellulose with PHA-leukocyte conditioned medium. In addition, the blastic cells in suspension culture strongly expressed phenotypic features which are characteristic of erythroblasts, in the presence of both PDS and 12-0-tetradecanoylphorbol 13-acetate (TPA), whereas they expressed features of megakaryoblasts in the presence of PDS alone. These results suggest that essential thrombocythemia is of myeloid stem cell origin. This is the first case in the literature in which a clonal evolution in ET has been followed closely, essential events were identified serially, and the blastic cells, which appeared as a result of the progression of ET, were found to have the capability to differentiate toward the three myeloid lineages.
authors.affiliation: Department of Internal Medicine, School of Medicine, Hiroshima University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Fujimoto
authors.forename: T
authors.initials: T
authors.lastname: Inada
authors.forename: N
authors.initials: N
authors.lastname: Imamura
authors.forename: N
authors.initials: N
authors.lastname: Oguma
authors.forename: H
authors.initials: H
authors.lastname: Kajihara
authors.forename: D M
authors.initials: DM
authors.lastname: Mtasiwa
authors.forename: O
authors.initials: O
authors.lastname: Katoh
authors.forename: K
authors.initials: K
authors.lastname: Fujimura
authors.forename: A
authors.initials: A
authors.lastname: Kuramoto
mesh_terms: D001752:Blast Crisis / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation; D003593:Cytoplasm / Q000648:ultrastructure; D004912:Erythrocytes / Q000473:pathology; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000473:pathology; D008875:Middle Aged; D010641:Phenotype; D013920:Thrombocythemia, Essential / Q000235:genetics / Q000276:immunology / Q000473:pathology*