Taylor Sundby’s quest to determine the effect of dominant negative nuclear factor Ya treatment on leukemic stem cell differentiation
Monday, November 10th, 2008To start I will give a quick summary of my overall goal… in following posts I will elaborate on the specifics and give updates as to how I am progressing.
So, without further ado the abstract:
Acute myelogenous leukemia (AML) patients accumulate a high number of malignant hematopoietic stem cells (HSCs) in their bone marrow. In their pathological state these cells are referred to as as leukemic stem cells (LSCs). The overcrowding of the bone marrow leads to decrease in red blood cells, platelets, or white blood cells (Lowenberg et al., 1999). AML correlates with the over-expression of the homeobox gene HoxB4 (Zhang et al., 2008). During hematopoiesis, HoxB4 expression is associated with positively regulating HSC proliferation (Zhu et al., 2005) while keeping HSCs in a primitive state by inhibiting their differentiation (Giannola et al., 2000). This study aims to reduce the LSC population by designing a dominant negative (DN) construct of NF-Ya protein, a HoxB4 transcription regulator. The purified DN NF-Ya will occupy the HOXB4 promoter by binding NF-Yb but will not induce HOXB4, thereby inhibiting HOXB4 expression in affected cells. We hypothesize, therefore, that DN NF-Ya treatment will reduce LSC populations in AML cells by inducing terminal differentiation in affected cells.