Maternal embryonic leucine zipper kinase (MELK) as a novel therapeutic target in the treatment of acute lymphoblastic leukemia

Acute Lymphoblastic Leukemia (ALL) is a hematological malignancy that affects children and young adults. Treatment is possible through chemotherapy and stem cell transplant, however there is still the risk of relapse and resistance. Although most children are cured, the cure rate in adults is very low. Hence, there is a need for novel therapeutic targets to improve outcome of ALL in adults. Maternal Embryonic Leucine Zipper Kinase (MELK) is a protein kinase that is found to be overexpressed in a variety of solid tumors. A recent study reported MELK to be a therapeutic target in Acute Myeloid Leukemia (AML). However, the role of this kinase in ALL is not well investigated. Previous studies showed FOXM1 to be a substrate for MELK. The downstream targets for FOXM1 include the Wnt/ β-catenin pathway. The Wnt pathway is known to be implicated in T-ALL. Hence, we hypothesized that MELK may act as a therapeutic target in ALL by inhibiting FOXM1 and subsequently, the Wnt/ β-catenin pathway. We found that MELK is overexpressed in ALL compared to mononuclear cells obtained from healthy donors. Inhibiting MELK kinase activity resulted in decreased cell viability. MELK inhibition decreased p-GSK3B and β-catenin. While these results suggest a possible role of MELK in the β-catenin signaling pathway, further studies are needed to establish the mechanism by which MELK affects β-catenin activity. MELK inhibitor is currently in trials for solid tumors as well as hematological malignancies. Hence, more research is needed to find the exact mechanism by which MELK inhibition is effective therapeutic approach in ALL.