Efficacy of the HOX-inhibitor HXR9 in acute myeloid leukemia

Abstract

Degree Project Thesis, Programme in Medicine. TITLE: Efficacy of the HOX-inhibitor HXR9 in acute myeloid leukemia. Mounting evidence suggests that transcription factors of the HOX family, previously best known for their role in embryogenesis, are involved in several other processes, among them hematopoiesis, and that overexpression can contribute to malignant transformation. Inhibition of HOX functions may be a potential treatment approach for hematopoietic malignancies. In this study we have investigated the effect of HXR9, a peptide designed to inhibit the interaction between HOX proteins and a cofactor, on acute myeloid leukemia (AML) cell lines in vitro. We show that AML-cells enter apoptosis when exposed to HXR9, in addition, the effect is dose-dependent but not specific to HXR9 as the negative control peptide CXR9 is also cytotoxic to the AML-cells, albeit to a lesser extent. Furthermore, we show that long time exposure to HXR9 may induce maturation in AML cells, though our results are inconclusive. Finally, we demonstrate that the cytotoxic efficacy and possibly pro-maturating effect is independent of the level of HOXA9 — a HOX protein commonly overexpressed in AML.