NEOPLASTIC HEMATOPOIETIC CELL GROWTH--INTERACTIONS WITH RETROVIRUSES

调节肽白细胞介素2（IL 2）与其特异性结合 受体是活化的T淋巴细胞生长的先决条件。 重组纯化的IL-2已被用于鉴定受体后事件 在介导IL 2功能中重要。 (Ca++）动员，蛋白激酶 C活化和磷酸肌醇水解都被发现与 IL 2诱导的基因激活。 IL 2激活的基因 包括IL 2受体、γ干扰素和 原癌基因c-fos、c-myb和c-myc。 IL 2受体的IL 2刺激 基因转录导致细胞表面受体的增加 对IL 2的亲和力低。 IL-2受体分布的进一步研究 已经表明它也在未成熟的胸腺细胞上表达， 单核细胞/巨噬细胞、肥大细胞和各种造血祖细胞 细胞 在这些细胞中，IL 2受体基因位于 造血生长因子的转录控制， 白细胞介素-3和粒细胞/巨噬细胞集落刺激因子。 对骨髓细胞分化的机制进行了研究， 分化 小鼠骨髓单核细胞白血病细胞系的变异体 例如WEHI-3BD+，其可以被诱导分化为 单核细胞/巨噬细胞和WEHI-3BD-对这些诱导剂无反应 被开发出来。 诱导无反应的细胞系分化为 1，25-二羟基胆钙化醇（1，25 (OH)2 D3），维生素D3的生物活性代谢产物。 的 两种细胞类型的分化都伴随着细胞分化的停止。 生长伴随着形态学和细胞化学性质的变化， 细胞。 这表明白血病细胞对 作用于细胞表面的分化剂保留了其 在对不通过质膜起作用的药剂的反应中分化 例如具有胞质/核受体的1，25（OH）2D 3。 调控 还在这些细胞系中研究了原癌基因转录。 c-fos、c-myc和c-myb的表达在亚克隆中是相同的， 细胞分化与否表明这些基因的表达 不足以诱导分化。

Binding of the regulatory peptide, interleukin 2 (IL 2) to its specific receptor is a prerequisite for activated T-lymphocytes to grow. Recombinant purified IL 2 has been used to identify post-receptor events important in mediating IL 2 function. (Ca++) mobilization, protein kinase C activation and phosphoinositol hydrolysis has all been found to correlate with IL 2 induced gene activation. The genes activated by IL 2 have included those for the IL 2 receptor, gamma interferon and the proto-oncogenes, c-fos, c-myb and c-myc. IL 2 stimulation of IL 2 receptor gene transcription results in an increase of receptors on the cell surface of low affinity for IL 2. Further studies of IL 2 receptor distribution has shown it also to be expressed on immature thymocytes, monocytes/macrophages, mast cells and a variety of hematopoietic progenitor cells. In these cells, the IL 2 receptor gene is under the transscriptional control of hematopoietic growth factors such as interleukin-3 and granulocyte/macrophage colony stimulating factor. Studies were conducted concerning the mechanism of myeloid cell differentiation. Variants of the murine myelomonocytic leukemia cell line such as WEHI-3B D+ which can be induced to differentiate into monocyte/macrophages and the WEHI-3B D- is unresponsive to these inducers were developed. The unresponsive cell line was induced to differentiate to granulocytes as well as monocytes by 1,25 dihydroxy-cholcalciferol (1,25 (OH)2 D3), the biologically active metabolite of Vitamin D3. The differentiation of both cell types was accompanied by cessation of cellular growth accompanies changes in morphologic and cytochemical properties of the cells. This suggests that leukemic cells unresponsive to differentiation agents acting at the cell surface retain their ability to differentiate in response to agents that do not act via the plasma membrane such as 1,25 (OH)2 D3 which has cytosolic/nuclear receptors. Regulation of proto-oncogene transcription was also studied in these cell lines. Expression of c-fos, c-myc and c-myb was identical in the subclones whether the cells differentiated or not suggesting that expression of these genes was not sufficient to induce differentiation.