A MODEL FOR SPONTANEOUS B-LINEAGE LYMPHOMAS IN IGHMU -HOX11 TRANSGENIC MICE

摘要: HOX11, a divergent homeodomain-containing transcription factor, was isolated from the breakpoint of nonrandom t(10;14)(q24;q11) chromosome translocation found in human T cell acute lymphoblastic leukemias. The places HOX11 coding sequence under transcriptional control TCR α/δ regulatory elements, resulting ectopic expression normal protein thymocytes. To investigate oncogenic potential we targeted its lymphocytes transgenic mice by placing cellular DNA Ig heavy chain or LCK sequences. Only IgHμ-HOX11 expressing low levels were viable. During their second year life, all became terminally ill with more than 75% developing large lymphomas spleen, which frequently disseminated to thymus, lymph nodes, and other nonhematopoietic tissues. Lymphoma cells predominantly clonal IgM+IgD+ mature B cells. Repopulation severe combined immunodeficient hyperplastic spleens indicated that tumor phenotype transplantable. Before development, transgene did not result perturbations lymphopoiesis; however, lymphoid hyperplasia involving splenic marginal zones present 20% spleens. Our studies provide direct evidence leads malignant transformation. These are useful model system study mechanisms involved transformation B-lineage lymphoma for testing novel approaches therapy. They represent animal non-Hodgkin’s peripheral origin.