Figure 6.
ENU treatment of mice receiving TEL2-BM transplants accelerates hematopoietic disease and causes T-cell lymphoma. (A) Kaplan-Meier survival curve of mice receiving transplants with bone marrow transduced with MSCV-IRES-GFP (MSCV-BM) or MSCV-TEL2-IRES-GFP (TEL2-BM) and treated with ENU 5 weeks after transplantation The mice receiving TEL2-BM transplants died 1.5 to 2 months earlier than the MSCV-BM mice, suggesting cooperation between TEL2 expression and ENU mutagenesis. (B) Spleen of a mouse with T-lymphoblastic lymphoma that underwent ENU treatment and TEL2-BM transplantation. The malignant lymphocytes in the red pulp express CD3 (brown color) while most of the lymphocytes associated with the follicular marginal zone do not express CD3 (anti-CD3 with cytoplasm/membrane localization, magnification × 40, marginal zone is on the left and the red pulp cells with CD3 expression are on the right). (C) The CD3+ malignant lymphocytes also expressed TdT (brown color), which is consistent with a lymphoblastic lymphoma (anti-TdT with nuclear localization, magnification × 40). (D) The T lymphocytes in the spleen do not stain with a GFP antibody; the only cells that are positive for GFP (bottom right corner) are B lymphocytes, which also stain positive for B220 (not shown). (E) Peripheral blood smear of a TEL2-BM/ENU mouse with increased WBCs (30 × 109/L [30 × 103/μL]) showing numerous dysplastic white cells (magnification × 100). (F) Blood smear of the same mouse stained with a CD3 antibody. Only a small percentage of cells (white arrowhead, red color) expressed this T-cell marker, indicating that the dysplastic cells are not of T-cell origin. The nucleated cells were counterstained with DAPI (blue color).