Acute myeloid leukemia (AML) encompasses a cytogenetically heterogeneous group of myeloid malignancies characterized by clonal expansion of abnormally or poorly differentiated myeloid cells in the bone marrow, blood and other tissues. Treatment failure, relapse and mortality of AML is unacceptably high and it is reasonable to predict that cure rates will not improve unless treatment modalities alternative to conventional chemotherapy and bone marrow transplantation are developed. A hallmark of AML is a failure to properly differentiate and the retinoic acid receptor (RAR) ligand all-trans-retinoic acid (ATRA) has demonstrated remarkable efficacy in inducing differentiation in a sub-type of AML, acute promyelocytic leukemia (APL). However, ATRA based treatment has failed to replicate this success in non-APL AML.

Our research is aimed towards the identification and characterization of mechanisms underlying the maturation arrest and ATRA-resistance of leukemic cells eventually enabling efficient therapy by induction of differentiation in all types of AML. We especially focus on epigenetic factors preventing the induction of myeloid differentiation by ATRA. Currently we investigate the roles of the lysine demethylase LSD1 and the lysine acetyltransferase GCN5.

Within this course we will test the effects of compounds inhibiting epigenetic modifiers as LSD1 and GCN5 on AML cells. We will assess cell growth using cell viability assays and perform FACS analyses measuring changes in myeloid differentiation and apoptosis markers following treatments. Further, we will perform basic analyses of RNA-seq data previously obtained.