Amélie De Maesschalck

Acute Myeloid Leukemia (AML) is a heterogeneous hematologic disease characterized by increased numbers of immature white blood cells called myeloblasts. At its core, AML is a disease of blocked differentiation. Cells fail to mature properly and instead continue to proliferate. Recent advancements in differentiation therapy have led to the approval of Revumenib, an anti-menin inhibitor. It triggers a massive differentiation event in AML cells, causing a brief spike in cell count, after which the leukemic cells die, ultimately leading to remission. Mechanistically, it breaks the interaction of MEN1 with methyltransferase 2A (KMT2A), which methylates lysine 4 of histone H3.
Non-terminally differentiated myeloid cells, mostly cells with a higher stemness, are the main drivers of this differentiation problem in AML and the proteins, histone posttranslational modifications (hPTMs) and metabolites work coordinately to define this molecular phenotype. ProGenTomics developed a multi-omics mass spectrometry (MS)-based approach that integrates these molecular fractions, extracted from one single cell pellet: the histone epigenome, metabolome and proteome. This approach was applied to a cohort of 18 AML cell lines in collaboration with Prof. Tim Lammens, yielding a coherent dataset that enables the identification of key molecular drivers of AML.
The aim of my PhD project is to apply our newly established multi-omics workflow to a timelapse experimental design to study causation during differentiation in 6 AML cell lines. I will induce differentiation through 6 different stimuli: two changing the histone epigenome, two the proteome, and two the metabolome. The starting point will be treatment with Revumenib. This will allow me to unravel the underlying dynamics following anti-menin therapy and pave the way for alternative therapies that attain differentiation through other biomolecular interventions.
 

• Master of Science in drug development
   

• Lab address: Ottergemsesteenweg 460, Building A, B-9000 Gent
• ProGenTomics
• Amélie De Maesschalck is interested to receive invitations for presentations or talks