From the Division of Molecular Carcinogenesis, Department of Medicine, Brander Cancer Institute, and Department of Pathology, New York Medical College, Valhalla, NY; Core Facility for Histopathology, Albert Einstein College of Medicine, Bronx, NY; Division of Hematology-Oncology, Mattel Children's Hospital, Department of Pathology and Laboratory Medicine, University of California at Los Angeles (UCLA) Jonsson Comprehensive Cancer Center, Molecular Biology Institute, David Geffen School of Medicine, Los Angeles, CA; and Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH.
The physiologic function of BUBR1, a key component of the spindle checkpoint, was examined by generating BUBR1-mutant mice. BUBR1–/– embryos failed to survive beyond day 8.5 in utero as a result of extensive apoptosis. Whereas BUBR1+/– blastocysts grew relatively normally in vitro, BUBR1–/– blastocysts exhibited impaired proliferation and atrophied. Adult BUBR1+/– mice manifested splenomegaly and abnormal megakaryopoiesis. BUBR1 haploinsufficiency resulted in an increase in the number of splenic megakaryocytes, which was correlated with an increase in megakaryocytic, but a decrease in erythroid, progenitors in bone marrow cells. RNA interference–mediated down-regulation of BUBR1 also caused an increase in polyploidy formation in murine embryonic fibroblast cells and enhanced megakaryopoiesis in bone marrow progenitor cells. However, enhanced megakaryopoiesis in BUBR1+/– mice was not correlated with a significant increase in platelets in peripheral blood, which was at least partly due to a defect in the formation of proplatelet-producing megakaryocytes. Together, these results indicate that BUBR1 is essential for early embryonic development and normal hematopoiesis.
A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis
A novel SHP-1/Grb2–dependent mechanism of negative regulation of cytokine-receptor signaling: contribution of SHP-1 C-terminal tyrosines in cytokine signaling
A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation
Allergen exposure–induced differences in CD34+ cell phenotype: relationship to eosinophilopoietic responses in different compartments
And a final message from antithrombin
Antiangiogenic antithrombin down-regulates the expression of the proangiogenic heparan sulfate proteoglycan, perlecan, in endothelial cells
Antibody-induced intracellular signaling works in combination with radiation to eradicate lymphoma in radioimmunotherapy
Anti-CD40L: biology and therapy in ITP
Cell adhesion: a partner for many
Chemokine receptor–8 (CCR8) mediates human vascular smooth muscle cell chemotaxis and metalloproteinase-2 secretion