Date of Award
Biochemistry & Molecular Biology
The five-year survival rate for patients with acute myeloid leukemia is 27.4%, with most patients who achieve temporary remission relapsing, despite chemotherapeutic treatments (National Cancer Institute, 2014). With the inadequacy of current drug therapies for human acute myeloid leukemia patients, the genetic changes in AML cells’ genomes and transcriptomes have been studied for insights as to more effective targeted therapies. Data obtained by the Roberts lab demonstrates that treatment of HL-60 cells with PMA, which leads to cell cycle arrest, differentiation and apoptosis, is accompanied by upregulation of approximately 100 transcription factor genes. For this project, the basic leucine zipper transcription factor, MAFB, was selected for further research exploration as a potential regulator of transcriptomic changes leading to reversal of the transformed phenotype of AML cells. MAFB was successfully overexpressed in HL-60 cells by transient transfection, eliciting the consequential upregulation of the putative gene targets TINAGL1 and IL1A. Quantified with RT-qPCR, the upregulation of TINAGL1 and IL1A from the overexpression of MAFB supports the hypothesis that MAFB elicits changes to the transcriptome that might drive differentiation. Additionally, MAFB was observed to significantly slow the division of HL-60 cells over the course of 60 hours, supporting the hypothesis that it plays a key role in inciting hematopoietic cell differentiation at the expense of cell cycle progression. These results justify further research on the transcriptional responses to MAFB overexpression, which are currently being explored by RNA-sequence analyses. It is the hope that the transcriptional changes mediated by MAFB will identify new targets of therapeutic consequence that could promote differentiation and/or cell cycle arrest.
Shofner, Tulley, "The Role of MafB in Reversing the Transformed Phenotype of Human Acute Myeloid Leukemia Cells" (2018). Dickinson College Honors Theses. Paper 312.