Lymphomagenesis is a mulitstep process in which the lymphoma cells become increasingly tumorigenic with time. In the initial phases of the disease, growth factor-dependent cells dominate; During the progression phases chromosome and oncogene rearrangements prevail. Leukemias possessing chromsomes or oncogene rearrangements have a poor prognosis compared to those lacking genetically-fixed rearrangements. Thus, it is of upmost importance to study the initial, growth-factor dependent phases of the disease so as to facilitate the design of rational approaches of intervention before gene rearrangementts occur. T leukemia/lymphomas of mice that are induced by radiation (an etiologic agent) initially comprise growth factor-dependent, autocrine cells. The nature of the growth factor (coined Lymphoma Growth Factor, LGF) and its cell surface receptor (LGF-R) will be studied by molecular cloning of genes encoding them. Molecular clones encoding the LGF and LGF-R will be studied on the nucleic acid and protein level. Antibodies specific for the LGF and LGF-R will be prepared. The site(s) at which LGF/LGF-R-positive cells first evolve in treated mice, as well as the characteristics of such cells will be studied. The existance and phenotypes of LGF/LGF-R-positive cells in non-treated mice will also be studied. Childhood Acute Lymphoblastic Leukemia of T cells (T-ALL) also appears to involve an LGF-dependent phase in which a growth factor similar to the murine LGF is implicated. Thus the study of the early, growth factor-dependent phase of murine lymphoma should further our understanding of childhood T-ALL as well.
