Abstract 1343: Tracking T cell leukemogenesis in mice with green fluorescence protein-labeled LSTRA leukemic cells

Abstract

Abstract LSTRA leukemia was originally induced in a BALB/c mouse by the Moloney murine leukemia virus. The established LSTRA leukemic T cell line is transplantable in BALB/c mice and serves as an important animal model for leukemogenesis. Numerous studies using LSTRA cells have been reported in the field of cancer therapy, including immunotherapy and chemotherapy. Subsequent identification of a lymphocyte-specific protein tyrosine kinase gene Lck in LSTRA cells further highlights the LSTRA leukemia as a key model in studying hematologic malignancy induced by oncogenic Lck protein tyrosine kinase. While intraperitoneal inoculation of LSTRA cells reproducibly induces leukemic death in syngeneic BALB/c mice, very little is known on the details of its malignant progression. It also is not clear if LSTRA leukemia in mice resembles any specific T cell leukemia in humans. To better understand the process of LSTRA leukemia, we engineered LSTRA cells to stably express green fluorescence protein (GFP) by retroviral transduction. GFP-labeled LSTRA cells are easily distinguishable by flow cytometry, immunofluorescence microscopy, and immunoblotting. Biochemical characterization confirms that, like the parental LSTRA leukemia, GFP-tagged LSTRA cells express high levels of active Lck kinase. Consistent with our previous report (J Immunol 159:5206), GFP-tagged LSTRA cells also exhibit constitutive activation of signal transducer and activator of transcription 3 (STAT3) and STAT5. BALB/c mice receiving 10 million GFP-labeled LSTRA cells intraperitoneally show signs of leukemia, such as acute weight loss, abdominal swelling, hunched posture, and squinting eyes, within 1 week. All mice die within 10 days. Even intraperitoneal inoculation of 50 GFP-labeled LSTRA cells results in 40% lethality within a month. By tracking GFP, we were able to identify multi-organ metastasis of LSTRA leukemia, including bone marrow, spleen, and liver. Immunohistochemistry analysis of tissue sections further revealed a unique concentration of LSTRA cells in the red pulp of spleen. It is important to note that mild to moderate lymphocytic infiltration of the spleen red pulp has been reported in patients with T cell large granular lymphocyte (LGL) leukemia. It suggests that LSTRA leukemia may represent a murine model of distinct human T cell maliganacy, such as LGL leukemia. All together, we have shown here that the GFP-labeled LSTRA cell line is a powerful tool to monitor leukemic progression in immune-competent mice. It has important implications in utilizing LSTRA leukemia for future studies in cancer therapy. Experiments are also in progress to define the molecular mechanisms underlying LSTRA infiltration in the spleen red pulp. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1343. doi:1538-7445.AM2012-1343