LEUKOCYTE REGULATORY MECHANISMS

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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)