Analysis Tools
neoplasm
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• mice show a modestly accelerated onset of spontaneous hematopoietic malignancy
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hematopoietic system
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• mice show perturbation in early T-cell differentiation
• percentages of double-negative precursor stage 3 (DN3) cells are reduced but their total numbers are not significantly reduced
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• mice have only 58% double-negative precursor stage 2 (DN2) cells compared with controls
• however, the numbers and percentages of downstream populations are not altered in the thymus
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• numbers of plasmacytoid dendritic cells are increased in the bone marrow
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• within the HPC-1 population, the percentage of FLT3hi cells is increased, suggesting an increase in lymphoid-based cells
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• 85% increase in the numbers of common lymphoid progenitor cells
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• analysis of LSK subsets shows a reduced number of hematopoietic stem cells (HSC)
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• the number of cells within the LSK stem and progenitor cell-enriched population is increased by 27% in the bone marrow
• however, no difference in bone marrow cellularity is seen
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• analysis of LSK subsets shows an increase in the heterogenous progenitor cell population HPC-1
• however, the numbers of multipotent progenitor cells and HPC-2 populations are not different
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• bone marrow cells from mutant mice repopulate the hematopoietic system of hosts more efficiently and retain stem cell capacity through serial transplantations
• enhanced hematopoietic reconstitution is due to increased production of differentiated progeny; HSCs show enhanced contribution to peripheral blood posttransplant and multipotent progenitor cells show enhanced contribution to peripheral leukocytes
• HSCs grown in culture show reduced proportion of self-renewing symmetric divisions and a trend toward higher proportion of differentiating divisions
• a reduced proportion of blast colonies and an increased proportion of differentiated colonies are produced from mutant bone marrow in vitro
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• increase in the percentages of Ki67+ cycling cells within the HSC, HPC-1 and overall LSK populations and higher percentages of these cells incorporate BrdU
• however, no changes in cell death are seen in hematopoietic stem cells or progenitor populations
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homeostasis/metabolism
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• modest increase in IFN-alpha levels in the plasma
• however, no differences in IFN-gamma or other cytokine levels are seen
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immune system
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• mice show perturbation in early T-cell differentiation
• percentages of double-negative precursor stage 3 (DN3) cells are reduced but their total numbers are not significantly reduced
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• mice have only 58% double-negative precursor stage 2 (DN2) cells compared with controls
• however, the numbers and percentages of downstream populations are not altered in the thymus
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• numbers of plasmacytoid dendritic cells are increased in the bone marrow
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• modest increase in IFN-alpha levels in the plasma
• however, no differences in IFN-gamma or other cytokine levels are seen
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endocrine/exocrine glands
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• mice have only 58% double-negative precursor stage 2 (DN2) cells compared with controls
• however, the numbers and percentages of downstream populations are not altered in the thymus
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cellular
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• increase in the percentages of Ki67+ cycling cells within the HSC, HPC-1 and overall LSK populations and higher percentages of these cells incorporate BrdU
• however, no changes in cell death are seen in hematopoietic stem cells or progenitor populations
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