The recent application of the high resolution banding technique to the study of ANLL chromosomes suggests that a much higher proportion of leukemias than the 50-60% recognized with conventional banding methods may carry chromosome abnormalities. We propose to investigate all newly diagnosed and previously untreated acute leukemia patients admitted to Memorial Hospital using high resolution banding methods in order to reevaluate relationships between chromosome change and tumor histology on the one hand and patient prognosis on the other. Results of recent cytogenetic and molecular genetic studies of neoplastic cells now enable the question of the significance of chromosome change to neoplastic development to be addressed more rigorously than has been possible in the past. Thus, in the case of immunoglobulin-producing human and murine B-cell tumors, cellular proliferation is associated with specific translocations which bring together chromosomal regions which may be involved with control of proliferation (presumptive onc genes) with those containing genes which encode function (immunoglobulin synthesis). Analysis of the transforming sequences isolated from a number of human tumor cell lines established their homology to transforming sequences of retroviruses. Other evidence points to enhanced expression of these onc genes in human tumors. The onc gene c-myc, the counterpart of the transforming RNA virus MC29 (v-myc), has been shown to become activated in the lymphoid cells of chicken when the long terminal repeat (LTR) sequence (which contains a viral promoter) integrates next to it leading to transcription of the onc gene, transformation and lymphoma development. This "promoterinsertion" mechanism of carcinogenesis provides a model for the consideration of the role of chromosome change, especially rearrangement (e.g., translocation) in the development of human tumors. Thus, a class of chromosome rearrangements may be visualized which bring together onc genes with either their promotors or determinants of target cell function leading to development of neoplasia. We propose to test these hypotheses by ascertaining the constitutive position of onc genes first in chromosomes from normal cells (of the germ line) and then in those of tumor cells in order to evaluate the significance of chromosome change in relation to onc gene sites. Gene mapping will be performed by in situ hybridization to chromosomes of onc genes and their cellular homologues cloned in appropriate vectors and labeled with 3H using methods developed by us for this purpose.