Kimura A, Fujimoto T, Inada T, Imamura N, Oguma N, Kajihara H, Mtasiwa D M, Katoh O, Fujimura K, Kuramoto A
Department of Internal Medicine, School of Medicine, Hiroshima University, Japan.
Cancer. 1990 Apr 1;65(7):1538-44. doi: 10.1002/1097-0142(19900401)65:7<1538::aid-cncr2820650715>3.0.co;2-3.
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.
一名57岁的原发性血小板增多症（ET）男性患者发展为骨髓纤维化，并进展至原始细胞转化状态。对原始细胞的特征进行了形态学、表型以及细胞培养方面的系列研究。在外周血中首次检测到的原始细胞具有髓系干细胞特征，并向巨核细胞系有轻微分化。然而，在病程后期，大多数原始细胞不成熟。在人血浆源性血清（PDS）存在的情况下进行培养时，最初阶段获得的一些原始细胞发生分化，形态上主要分化为粒细胞和巨噬细胞，但后来倾向于分化为巨核细胞和巨噬细胞。最终，原始细胞似乎失去了形态学分化能力。然而，当在含PHA - 白细胞条件培养基的甲基纤维素中培养时，这些原始细胞形成了由成红细胞、粒细胞、巨噬细胞和未成熟原始细胞组成的混合集落。此外，在悬浮培养中，原始细胞在PDS和12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）同时存在时强烈表达成红细胞特征性的表型特征，而在仅存在PDS时表达巨核母细胞特征。这些结果提示原发性血小板增多症起源于髓系干细胞。这是文献中首例对ET的克隆进化进行密切追踪、连续确定关键事件，并发现因ET进展而出现的原始细胞具有向三种髓系谱系分化能力的病例。
