mortality/aging
• mice treated with pI:pC and ENU die rapidly between 2 and 10 months coincident with tumor presentation
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neoplasm
• 47% of 5-10 week old mice treated with pI:pC then treated with ENU develop hematopoietic neoplasms 2-10 months after treatment
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• some pI:pC and ENU treated mice develop thymic derived T cell lymphoblastic lymphomas (17%)
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• some pI:pC and ENU treated mice develop granulocytic sarcoma/acute myeloid leukemia (30%)
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• some pI:pC and ENU treated mice develop granulocytic sarcoma/acute myeloid leukemia (30%); these are solid masses of proliferating myeloblasts which form in retroperitoneum, soft tissue, or in bones of sternum, cranium, or extremities adjacent to soft tissue
• tumor cells disseminate widely, with clusters of cells found in spleen, liver, kidney and lymph nodes
• in some mice, increased myeloblasts are observed in bone marrow, as well as markedly increased white blood cell counts with identifiable circulating leukemic blasts
• tumors are transplantable
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endocrine/exocrine glands
• some pI:pC and ENU treated mice develop thymic derived T cell lymphoblastic lymphomas (17%)
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hematopoietic system
N |
• mimimal abnormalities in hematopoiesis are observed in mutants expressing the Runx1 knock-in allele after pI:pC treatment, although a slight increase in granulocyte-monocyte, mixed and total colonies, as well as in day 12 CFUs in bone marrow, is seen
• no leukemia develops during the first 11months of life of treated mutants
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• 2 mice develop hematopoietic neoplasms by 1 year of age (1 T cell lymphoma, 1 undifferentiated lymphoma)
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• some pI:pC and ENU treated mice develop thymic derived T cell lymphoblastic lymphomas (17%)
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cellular
• bone marrow cells isolated from mice treated with pI:pC show enhanced replating efficiency in culture; cells are able to form myeloid colonies long after wild-type cells have stopped growing
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immune system
• some pI:pC and ENU treated mice develop thymic derived T cell lymphoblastic lymphomas (17%)
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