Dissecting the role of Mixed-Lineage-Leukemia 5 (MLL5) in the DNA damage response and its potential effects on leukemogenesis (A02)

• Subject Area: Immunology ; Hematology, Oncology
• Term: from 2012 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 217328187

Heterozygous loss of Mll5/MLL5 results in significantly elevated intracellular levels of Reactive Oxygen Species (ROS) in mouse hematopoietic stem/progenitor cells (HSPCs) and primary human AML cells. Using a xenograft/NSG mouse model and oral administration of an effective antioxidant, we want to evaluate the effects of elevated ROS in primary human AML samples with 7q-deletions (i.e. heterozygous loss of MLL5) with respect to their survival, malignancy, engraftment potential and genetic evolution. In a second line of study, we propose to conduct experiments to identify genetic and environmental events potentially cooperating with Mll5-deficiency to trigger overt leukemia. Finally, using a set of molecular tools generated during the first funding period, we wish to dissect Mll5 function in DNA repair and ROS induction at the molecular level.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1074: Experimental Models and Clinical Translation in Leukemia
• Applicant Institution: Universität Ulm
• Project Head: Professor Dr. Hans-Jörg Fehling