A 25-year-old man noted swelling of the right cervical lymph nodes in October 1983. Diagnosis of malignant lymphoma was made on the basis of pathological examination of biopsies. Despite both chemotherapy and irradiation treatment, blast cells appeared in the peripheral blood and bone marrow in April 1984. Immunophenotypic analysis demonstrated that the blasts in the patient's peripheral blood expressed CD13, CD33, CD41a, and no markers for T or B lymphocytes, suggesting that he had been suffering from megakaryocytic sarcoma. We established a new cell line derived from the blasts in the peripheral blood, designated KH184. KH184 cells expressed glycoprotein (GP) Ib (CD42b) and GPIIb/IIIa (CD41a), while platelet peroxidase (PPO) activity was negative in an ultrastructural study. Both Northern blot and flow cytometric analysis of surface antigens and DNA content revealed that treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) did not induce the maturation of these cells. Various cytokines such as interleukin 3 (IL-3), interleukin 6 (IL-6), and leukemia inhibitory factor (LIF) had no effect in promoting the growth of KH184 cells. KH184 cells expressing CD41a seem to possess unusual characteristics. KH184 cells, human GPIIb- and GPIIIa-positive leukemia cells, which lack response to TPA-induced differentiation, provide a new and unique model for the characterization of factors that are implicated in the terminal differentiation of megakaryocytes, and should aid in studies of the mechanism underlying the occurrence of megakaryocytic sarcoma.
Tiaramide in 10(-4) or 10(-5) M depressed the ADP-induced aggregation of rabbit platelets using the turbidimetric method. In modified Chandler's loop method, tiaramide in the same concentration accelerated the restoration of the time course of disaggregation.
Regulation of interleukin-3 receptor (IL-3R) gene expression by tumor necrosis factor alpha (TNF alpha) was investigated using an IL-3-dependent CD34-positive hematopoietic cell line (KMT2) and a human megakaryocytic cell line (CMK). KMT2 expressed IL-3R alpha-subunit mRNA, whereas the level of expression of IL-3R beta-subunit mRNA was low. CMK expressed IL-3R beta-subunit mRNA more strongly. The expression of IL-3R mRNA varied in the progenitor cells of different lineages. TNF alpha markedly enhanced expression of IL-3R beta-subunit mRNA in KMT2, whereas it only slightly augmented IL-3R alpha-subunit mRNA level. TNF alpha weakly augmented IL-3R mRNAs in CMK. However, the enhancement of IL-3R beta-subunit mRNA in CMK was hardly detectable. The effects of TNF alpha on IL-3R mRNA expression were completely different in a primitive and in a more committed hematopoietic cell line. Addition of TNF alpha to KMT2 resulted in increased numbers of IL-3R on the cell surface without increased IL-3R affinity. The combination of IL-3 with TNF alpha abolished TNF alpha-induced inhibition of proliferation of KMT2. These results indicate that TNF alpha modulates the IL-3-responsiveness of primitive hematopoietic cells through up-regulation of the expression of IL-3R mRNAs, especially that of IL-3R beta-subunit mRNA. Phorbol ester (TPA) enhanced the IL-3R mRNA expression in KMT2.(ABSTRACT TRUNCATED AT 250 WORDS)
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