Growth and differentiation of two human megakaryoblastic cell lines; CMK and UT-7

We showed that these two cell lines obviously expressed megakaryocytic phenotypes, such as multilobular, hyperploid nuclei, expression of GPIIb/IIIa complex, GPIb and PPO, although they have been originated from patients with leukemia. Furthermore, these cells had following characteristics. First, they responded to various kinds of hemopoietic factors. Especially, UT-7 cells were solely dependent on GM-CSF, IL-3 or Ep. Therefore UT-7 cells are useful to the assay of these factors as megakaryocytic cells. These facts provide us with new questions: why they are dependent on plural number of factors? How are the expressions of their receptors controlled. Is there an "autocrine" mechanism controlling their growth? Among these questions, we have just started with the Ep receptors, and most of the problems remain to be clarified. Second, PMA treatment suppressed their growth, but enhanced their differentiation and maturation. Among the megakaryocytic phenotypes, increase in GPIIb/IIIa complex, determined by a biochemical method, PPO by ultrastructural study, and the increase in cellular ploidy were clearly observed by PMA treatment. The phorbol ester PMA is well known to induce the differentiation of various kinds of leukemic cells (Rovera et al., 1979). Detailed molecular basis to clarify why the same PMA treatment causes differentiation into different cell lineages, dependent on cellular origin of the target cells, should be further studies. Third, the cells produced hemopoietic growth factors by PMA treatment, the majority of which was GM-CSF. Humoral control of megakaryopoiesis still remains unsettled. Our study may shed a light on its "multistep" regulatory mechanisms. Availability of a large amount of homogeneous megakaryocytic populations, which are responsive to hemopoietic factors and phorbol ester, will provide us with a great deal of informations concerning the molecular insight of megakaryocytopoiesis and thrombocytopoiesis.