Individuals with NQO1P187S mutation have no detectable NQO1 protein levels. These individuals have been extensively predicted to be at high risk for developing chemotherapy-induced leukemia. We have studied the effect of Etoposide, a DNA Topoisomerase II inhibitor used in many chemotherapeutic regimens, on NQO1 gene deleted (NQO1-/-) mice. NQO1-/- mice are born with a myelodysplastic bone marrow. Flow cytometric analysis of blood, bone marrow and spleen showed an increase in megakaryocytic and myeloid cell lineages in NQO1-/- mice. A spectrum of responses ranging from leukopenia to myeloid leukemia were observed with increasing drug concentration by Flow cytometry and confirmed by histochemistry in NQO1-/- mice. C/EBPalpha plays a key role in the myeloid lineage commitment of hematopoietic progenitor cells. NQO1 protects C/EBPalpha from 20S proteasomal degradation in in vitro assays. Altered C/EBPalpha levels are responsible for the preferential increase in myeloid cell lineage in NQO1-/- mice.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 402.