mortality/aging
• fewer than expected mice are present at weaning
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hematopoietic system
• bone marrow cells from pIpC-induced mice form fewer granulocyte-macrophage positive colonies than when wild-type cells are used
• bone marrow cells transplanted into wild-type mice and induced with pIpC fail to reconstitute multiple hematopoietic lineages
• however, treatment with imatinib restores the ability of pIpC-treated bone marrow cells to induce long-term multiple lineages reconstitution in transplantation experiments
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• bone marrow cells from pIpC-induced mice form fewer granulocyte, erythrocyte, macrophage, and megakaryocyte positive colonies than when wild-type cells are used
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• all pIpC-induced mice develop a chronic myelocytic leukemia (CML)-like myeloproliferative disease
• bone marrow cells activated with pIpC induce develop a CML-like myeloproliferative disease when transplanted into wild-type mice
• however, secondary transplantation of neoplastic cells or fractionated splenocytes are highly inefficient at inducing myeloproliferative disease
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• in pIpC-induced mice
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• 2 weeks after pIpC induction, bone marrow and spleens exhibit a decreased in the frequency of lymphoid and erythroid lineages but an increase in myeloid lineages compared to control mice
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• in pIpC-induced mice despite treatment with imatinib
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• after pIpC induction, mice exhibit severe myeloid leukocytosis with a 25-fold increase in white blood cells compared with similarly treated wild-type mice
• however, treatment with imatinib reduces white blood cell counts to wild-type levels
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• the number of Mac1+Gr1+ myeloid cells in the spleen and bone marrow of pIpC-induced mice is increased compared to in wild-type mice
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• severe following pIpC induction
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• the frequency of hematopoietic stem cells in the bone marrow of pIpC-induced mice is decreased compared to in wild-type mice
• the number of hematopoietic stem cells in the bone marrow of pIpC-induced mice is less than in wild-type mice
• bone marrow cells transplanted into wild-type mice and activated with pIpC inhibit normal bone marrow hematopoietic stem cells and result in a decrease in donor and recipient-type hematopoietic stem cells compared to when wild-type bone marrow cells are transplanted
• however, treatment of pIpC-induced mice with imatinib returns the frequency of hematopoietic stem cell to near normal even in transplantation experiments
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• the absolute number of hematopoietic stem cells in the spleen is increased in pIpC-induced mice compared to in wild-type mice
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• pIpC-induced mice exhibit splenic architecture effacement unlike similarly treated wild-type mice
• however, treatment with imatinib returns spleen architecture to normal
• 2 weeks after pIpC induction, bone marrow and spleens exhibit a decreased in the frequency of lymphoid and erythroid lineages but an increase in myeloid lineages compared to control mice
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• 10-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
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• following pIpC induction
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• in pIpC-induced mice
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• in pIpC-induced mice
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• pIpC-induced mice loss organized splenic follicle cells unlike similarly treated wild-type mice
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• when bone marrow cells are transplanted into recipient mice and induced with pIpC recipient mice exhibit enlarge spleen, effacement of spleen architecture, and increased white blood cell counts compared to when mice are transplanted with control bone marrow cells lacking the cre transgene
• however, treatment with imatinib decreased white blood cell counts in recipients following pIpC-induction of transplanted bone marrow cells
• bone marrow cells transplanted into wild-type mice and activated with pIpC inhibit normal bone marrow hematopoietic stem cells and result in a decrease in donor and recipient-type hematopoietic stem cells compared to when wild-type bone marrow cells are transplanted
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neoplasm
• neoplastic cells in the livers and spleens of pIpC-induced mice are positive for proliferative markers
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• 25% of un-induced mice develop a chronic myelocytic leukemia (CML)-like disease unlike control mice
• pIpC-induced mice exhibit a CML-like myeloproliferative disease unlike similarly treated wild-type mice
• bone marrow cells activated with pIpC induce develop a CML-like myeloproliferative disease when transplanted into wild-type mice
• however, secondary transplantation of neoplastic cells or fractionated splenocytes are highly inefficient at inducing myeloproliferative disease
• treatment with imatinib increases the frequency of leukemia initiating cells in transplantation experiments with pIpC-activated whole bone marrow cells and hematopoietic stem cells and results in greater incidence of CML-like disease
• leukemia cells infiltrate the lungs in pIpC-induced mice
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liver/biliary system
• pIpC-induced mice exhibit mature myeloid cells surrounding portal cavities and infiltrating the parenchyme unlike in similarly treated wild-type mice
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• 2-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
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• following pIpC induction
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• pIpC-induced mice exhibit mature myeloid cells infiltrating the parenchyme unlike in similarly treated wild-type mice
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respiratory system
• pIpC-induced mice exhibit mature myeloid cells infiltrating the lungs unlike in similarly treated wild-type mice
• leukemia cells infiltrate the lungs in pIpC-induced mice
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immune system
• all pIpC-induced mice develop a chronic myelocytic leukemia (CML)-like myeloproliferative disease
• bone marrow cells activated with pIpC induce develop a CML-like myeloproliferative disease when transplanted into wild-type mice
• however, secondary transplantation of neoplastic cells or fractionated splenocytes are highly inefficient at inducing myeloproliferative disease
|
• after pIpC induction, mice exhibit severe myeloid leukocytosis with a 25-fold increase in white blood cells compared with similarly treated wild-type mice
• however, treatment with imatinib reduces white blood cell counts to wild-type levels
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• the number of Mac1+Gr1+ myeloid cells in the spleen and bone marrow of pIpC-induced mice is increased compared to in wild-type mice
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• severe following pIpC induction
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• pIpC-induced mice exhibit splenic architecture effacement unlike similarly treated wild-type mice
• however, treatment with imatinib returns spleen architecture to normal
• 2 weeks after pIpC induction, bone marrow and spleens exhibit a decreased in the frequency of lymphoid and erythroid lineages but an increase in myeloid lineages compared to control mice
|
• 10-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
|
• following pIpC induction
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• in pIpC-induced mice
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• in pIpC-induced mice
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• pIpC-induced mice loss organized splenic follicle cells unlike similarly treated wild-type mice
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growth/size/body
• 2-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
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• following pIpC induction
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• 10-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
|
• following pIpC induction
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• in pIpC-induced mice
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