LEUKOCYTE REGULATORY MECHANISMS

在继续广泛关注各种因素的情况下， 影响白细胞增殖和分化，具体研究 将努力：（1）继续探讨有关机制， 在短期培养中调节人淋巴细胞增殖;以及 (2)进一步阐明细胞遗传学异常的作用（ 涉及的特定染色体和畸变类型）， 人类白血病前期疾病的发生和随后的演变， 非典型急性白血病 对于正常淋巴细胞的研究，我们将强调 可溶性生长因子（白细胞介素）在促分裂原刺激和 抗原刺激的培养物，特别是刺激性和抑制性的 影响T细胞增殖的因素。 这些调查将 利用暴露于各种因素的正常人淋巴细胞的培养物， 与不同的有丝分裂原和抗原结合，现在正在 扩展到包括对细胞周期特异性基因表达的影响。 对于染色体研究，我们将扩展和拓宽现有的 白血病前期疾病的长期研究及其预后和生物学效应 特定细胞遗传学疾病的意义。 这些调查将 不仅有临床应用，而且还将扩展我们对 基因改变在人类进化过程中的重要性 人类肿瘤细胞群的数量。 在一项相关研究中，我们将探讨 非典型染色体脆性的家族性模式及其与 白血病前期和白血病的风险。（高频）

Within the context of a continuing broad interest in various factors influencing leukocyte proliferation and differentiation, specific studies will attempt to: (1) continue to explore mechanisms involved in the regulation of human lymphocyte proliferation in short-term cultures; and (2) further delineate the role of cytogenetic abnormalities (both the specific chromosomes involved and the types of aberrations) in the initiation and subsequent evolution of human preleukemic disorders and atypical acute leukemia. For the studies of normal lymphocytes, we will emphasize the role of soluble growth factors (interleukins) in both mitogen-stimulated and antigen-stimulated cultures, and particularly stimulatory and inhibitory factors influencing T-cell proliferation. These investigations will utilize cultures of normal human lymphocytes exposed to various factors in combination with different mitogens and antigens, and are now being extended to include effects on expression of cell-cycle specific genes. For the chromosome studies, we will extend and broaden an existing long-term study of preleukemic disorders and the prognostic and biologic significance of specific cytogenetic disorders. These investigations will not only have clinical applications but will also extend our understanding of the significance of genetic alterations in the initiation and evolution of human neoplastic cell populations. In a related study, we will explore familial patterns of atypical chromosomal fragility and its relationship to the risk of preleukemia and leukemia. (HF)