Lyn Tyrosine Kinase Signals Cell Cycle Arrest in Mouse and Human B-Cell Lymphoma

Abstract

Tumor dormancy is an operational term used to describe a prolonged quiescent state in which tumor cells are present, but tumor progression is not clinically apparent. In order to study the mechanisms underlying tumor dormancy, we have utilized two murine models of dormancy with an aggressive murine B-cell lymphoma (BCL₁) [1–3]. In the first model, BALB/c mice are immunized to the idiotype (Id) of the BCL₁ immunoglobulin (Ig) before challenge with BCL₁. In the second model, antibody to various epitopes on the BCL₁ Ig (an IgM-λ) are injected into SCID mice before or after challenge with BCL₁. In naive BALB/c or SCID mice, the tumor grows primarily in the spleen and splenomegaly is detected approximately one month after challenge with 3 x 10⁴10⁶ BCL₁ cells. In Idimmune mice injected with 10⁶ BCL₁, 70% do not develop splenomegaly by day 60. We have used this time period as an arbitrary cut-off and have considered such mice to harbor dormant tumor. When the spleens of Id-immunized BALB/c mice that display tumor dormancy are examined, a population of dormant lymphoma cells (DLC) can be isolated by multiparameter cell sorting. The rarity of λ light chain in BALB/c mice (usually less than 0.5%) has facilitated isolation of the DLC. Examination of these cells shows that they are physiologically different from those of BCL₁ cells growing in non-immune BALB/c.