GLUCOCORTICOID-RESISTANT LEUKEMIC LYMPHOCYTES

这些研究有两个总的目标，都与使用 糖皮质激素治疗白血病和淋巴瘤。 一个目标是 应用和扩展我们对糖皮质激素受体和机制的知识 作用于正常和恶性淋巴细胞及相关细胞。 为这些 研究我们正在应用我们最近开发的minicolumn程序， 胞质溶胶中非活化、活化和部分受体复合物的分析 在不同的条件下从上述细胞中分离。 特定电流的 我们感兴趣的是稳定钙蛋白酶抑制蛋白受体的作用， 天然存在的钙激活蛋白家族的蛋白抑制剂 称为钙蛋白酶的蛋白酶 我们发现， 慢性淋巴细胞性白血病患者细胞胞浆中的受体 与急性非淋巴细胞白血病（CLL）患者相比， 白血病（ANLL）至少部分是由于前者细胞的存在， 一种类似钙蛋白酶抑制剂的稳定剂 另一个目标是扩大我们对糖皮质激素对 淋巴细胞和其他细胞通过抑制或 与淋巴因子如白细胞介素2（IL-2）和免疫或 γ干扰素 我们已经证明，γ干扰素是主要的 增加人单核细胞上IgG Fc受体的淋巴因子， 糖皮质激素与γ干扰素一起增加这种作用， 以及抗体依赖性和非依赖性肿瘤细胞裂解和表达 I类和II类HLA抗原。 我们正在调查 这些影响的机制。 与IL-2相关，自分泌机制 肿瘤生长涉及IL-2的产生和反应， 在MLA 144中建立，MLA 144是一种产生IL-2的白血病细胞系，来源于 巨猿 （丁）

These studies have two general goals, both related to the use of glucocorticoids in treatment of leukemias and lymphomas. One goal is to apply and extend our knowledge of glucocorticoid receptors and mechanisms of action to normal and malignant lymphocytes and related cells. For these studies we are applying our recently developed minicolumn procedure to the analysis of nonactivated, activated, and meroreceptor complexes in cytosols from the cells mentioned under various conditions. Of particular current interest to us is the role in stabilizing receptors of calpastatin, a naturally occurring protein inhibitor of a family of calcium-activated proteases called calpains. We have found that the relative stability of receptors in cytosols from cells of patients with chronic lymphocytic leukemia (CLL) compared to those from patients with acute nonlymphocytic leukemia (ANLL) is at least partly due to the presence in the former cells of a stabilizer that closely resembles calpastatin. The other goal is to extend our observations on glucocorticoid effects on lymphocytes and other cells that are mediated by inhibition of, or synergism with, lymphokines such as interleukin 2 (IL-2) and immune or gamma interferon. We have shown that gamma interferon is the major lymphokine that increased Fc-Receptors for IgG on human monocytes, and that glucocorticoids added together with gamma interferon augment this effect as well as antibody-dependent and\-independent tumor cell lysis and expression of class I and class II HLA antigens. We are now investigating the mechanisms of these effects. In relation to IL-2, an autocrine mechanism of neoplastic growth involving IL-2 production and response has been established in MLA 144, an IL-2 producing leukemia cell line derived from a Gibbon ape. (D)