hematopoietic system
• clonogenic capacity of hematopoietic precursors is reduced, however, the number of clusters in bone marrow and spleen cultures is increased compared to wild-type cultures
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• disruption of myeloid hematopoiesis, with mutants developing a myeloproliferative disorder by 12 months of age, characterized by accumulation of myeloid precursors, including promyelocytes, in the bone marrow, that infiltrate the spleen, the lymph nodes, and the thymus
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• clonogenic capacity of hematopoietic precursors is reduced, particularly the number of BFU-E
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• mutants with leukemia show an increase in white blood cell counts in the peripheral blood
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• an increase in granulocyte/lymphocyte ratio is seen in the peripheral blood of some mutants
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immune system
• disruption of myeloid hematopoiesis, with mutants developing a myeloproliferative disorder by 12 months of age, characterized by accumulation of myeloid precursors, including promyelocytes, in the bone marrow, that infiltrate the spleen, the lymph nodes, and the thymus
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• mutants with leukemia show an increase in white blood cell counts in the peripheral blood
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• an increase in granulocyte/lymphocyte ratio is seen in the peripheral blood of some mutants
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mortality/aging
• due to leukemia
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neoplasm
• about 10% of mutants develop overt acute leukemia after they reach 1 year of age
• retinoic acid markedly increases the terminal differentiation of leukemic cells to a larger extent than wild-type hematopoietic precursors, indicating an increased sensitivity of leukemic blasts to the differentiating action of retinoic acid
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• leukemia is characterized by accumulation of promyelocytes in the bone marrow, peripheral blood, and spleen, indicative of acute promyelocytic leukemia
• some promyelocytes in the leukemia show the presence of pathognomonic cytoplasmic Auer's bodies
• leukemic cellular proliferation retains the ability to terminally differentiate toward mature granulocytes
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