Margaret Colton

School: The University of Chicago

Major: Biological Sciences

DOI: https://doi.org/10.21985/n2-yakh-d032

Maggie is a recent graduate of the University of Chicago where she studied Biology with a specialization in Cancer Biology. She will be pursuing a PhD in Pharmacology from the University of California - San Francisco where she looks forward to continuing her cancer focus and studying cancer treatment. Outside of the lab, she enjoys playing music, baking and riding her bike along Lake Michigan.

MELK Inhibition in MLL-rearranged ALL

Abstract

MLL-rearranged Acute Lymphoblastic Leukemia is a subset of leukemia characterized by a translocation of the MLL gene and an aberrant gene expression profile. Patients with this type of ALL face a poorer prognosis and limited treatment options. One possible target for treatment is FLT3, a receptor tyrosine kinase frequently upregulated in MLL-r ALL. Attempts to treat MLL-r ALL by inhibiting FLT3 expression have demonstrated some efficacy but fail to achieve results at clinically relevant doses. This study investigates the efficacy of OTS167, an inhibitor of MELK, which has been shown to downregulate the expression of FLT3 in other types of leukemia. In MLL-r ALL, OTS167 diminished cell viability at clinically relevant doses, and downregulated FLT3 in a post-transcriptional manner. Knockdown of MELK by siRNA also downregulated FLT3 expression, however knockdown of FLT3 failed to show any effect on cell viability. These findings indicate that OTS167 may have clinical efficacy in MLL-rearranged ALL but that the mechanism of action may not by FLT3-mediated.