Antigen Receptor Signaling Induces Differential Tyrosine Kinase Activation and Population Stability in B-Cell Lymphoma

Abstract

Cancer dormancy is a phenomenon where neoplastic cells exist within a host without progressive growth (1–3). Clinical examples of dormancy in humans can be found in cases of melanoma (4, 5), breast carcinoma (6), and lymphoma [R. Levy personal communication]. To identify potential mechanisms regulating cancer dormancy, a murine lymphoma model has been established. This dormancy model system utilizes a mouse B-cell lymphoma, BCL₁, whose aggressive growth normally leads to rapid splenomegaly, late onset leukemia, and eventual death within 30 days after challenge. However, the development of splenomegaly and subsequent disease can be prevented by immunization of syngeneic recipients with membrane immunoglobulin (mlg) purified from BCL₁, prior to challenge. Seventy percent of immunized animals do not develop tumor by 60 days and in some cases can survive up to 2 years, the lifespan of a normal animal. Dormancy established in these animals is not simply the elimination of BCL₁ by the host immune system because BCL₁, can be specifically detected using polymerase chain reaction and can be isolated using flow cytometry from the spleen of dormant animals. Adoptive transfer of splenocytes from dormant animals to naive recipients results in regrowth of the tumor (7), and is further evidence that BCL₁, cells are present.