AuthorEssif, Jacob Nathaniel
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PublisherThe University of Arizona.
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EmbargoRelease after 05/09/2021
AbstractDiffuse large B-cell lymphoma (DLBCL) accounts for thirty-one percent of B-cell Non-Hodgkin lymphomas (NHL) diagnosed in the United States (16). The current treatment is a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (24). However, relapses do still occur (39). As previously shown, this may be due to therapy induced polyploidy (39). Treatment with alisertib, an aurora A kinase (AURKA) inhibitor, has been shown to result in polyploid cells that are able to re-enter the cell cycle (39). The formation of polyploid cells that are resistant to the current standard of care and that are able to reform tumors has been proposed as one of the mechanisms behind the relapses seen in patients with DLBCL. Previous genomic and proteomic analysis of these polyploid cells showed an increase in the levels of TPX2 (39), a protein that interacts with AURKA during mitosis (31). AurkinA is a small molecule that has been shown to inhibit the interaction between AURKA and TPX2 (42). We propose that inhibition of the interaction between AURKA and TPX2 in conjunction with AURKA inhibition will abrogate treatment induced polyploidy in DLBCL.
Degree ProgramGraduate College
Cellular and Molecular Medicine