By Icon Health Publications
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Additional info for Aplastic Anemia - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References
Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 15-JUL-1998; Project End 30-NOV-2007 Summary: (provided by applicant): The homozygous NQO1*2 polymorphism results in a total lack of NQO1 activity due to accelerated degradation of the mutant NQO1*2 protein by the ubiquitin/proteasomal pathway. The NQO1*2 polymorphism has been found to be a risk factor for benzene-induced myeloid toxicity but also for childhood and adult de-novo leukemias and secondary leukemias arising as a result of chemotherapy.
Enzymes that are pertinent to this investigation include cytochrome P-450, myeloperoxidase and those of the mitochondrial electron transport chain. Based on this hypothesis, the specific aims of this project will continue to: investigate biochemical and molecular interactions of BPderived quinones and BP-7,8-dihydrodiol (BP-diol) which occur as a result of their interactions with organelles and enzymes from bone marrow cells; investigate the mechanisms of toxicity of BP and its metabolites to DBA/2 bone marrow stromal cells in vitro and in vivo; examine the ability of BP and its metabolites to alter the differentiation of human myeloid cell lines, ML-1 and HL-60, and progenitor cells from DBA/2 mice; and evaluate if a peroxide-dependent mechanism is involved in the bioactivation of BPdiol in vitro and in vivo.
The effect of over- expressing Hox genes on the hematopoietic Studies 31 development of normal and Pbx1 deficient progenitors and ES cells will be studied. Differences between normal and Pbx1 deficient ES cells in terms of in vitro differentiation or susceptibility to Hox over-expression will form the basis of an assay for Pbx1/Hox function. By defining the specific requirements for Pbx1 function in normal hematopoiesis, these experiments will further our understanding of the molecular pathogenesis of leukemia, aplastic anemia and myelodysplasia.
Aplastic Anemia - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References by Icon Health Publications