The c-myc proto-oncogene appears to play an important role in the malignant transformation of hematopoietic cells. Two of the most striking examples of this is the activation of the c-myc oncogene by chromosome translocation into the context of an immunoglobulin gene system in Burkitt's lymphoma and mouse plasmacytomas. While both of these cells are immunoglobulin producing cells, the mouse plasmacytoma represents a more mature B-cell. In human B-cell malignancies, plasma cell leukemia is the most similar cell type to the mouse plasmacytoma. Using the mouse tumor as a model, it is important to examine tumors from patients with plasma cell leukemia to determine if similar molecular events occur that lead to malignant transformation. We have begun our studies by examining the c-myc gene in a patient that presented to the NMOB with an IgAK producing plasma cell leukemia. Our initial studies on DNA from this patient's tumor cells revealed a rearrangement of the c-myc proto-oncogene. This rearrangement appears to have occurred on the 3' side of the c-myc gene and in this respect is similar to the variant translocations observed in Burkitt's lymphoma [Blood, 67:1542(1986)]. Northern analysis of RNA from this tumor indicated high level of expression of the c-myc proto-oncogene. Thus, in this patient's tumor the c-myc proto-oncogene appears to have been activated by a chromosome rearrangement. We intend to investigate in detail the molecular events that have led to an alteration of the c-myc gene in this tumor. These studies will include the nature and position of the rearrangement, the identification of the DNA introduced by the rearrangement, the mechanism of the activation of the c-myc gene and the relationship of these molecular events to the transformation of this cell. Based on these studies, we intend to extend this analysis to other human plasma cell leukemias in an attempt to understand the steps involved in malignant transformation in this cell type.