Identification and mechanism of human peptides protecting against therapy-induced leukemia (B05)

• Subject Area: Biophysics ; Hematology, Oncology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 316249678

Induction of secondary leukemias by chemotherapy-based cancer treatment represents a serious side effect that frequently involves endonuclease G (EndoG)-mediated chromosomal rearrangements at the mixed-lineage leukemia (MLL) gene. The applicants identified peptides antagonizing such rearrangements and found that they differentially affect MLL binding of EndoG, which operates in mitochondria in unstressed cells. In the 2nd funding period, they will characterize differences in peptide mode-of-action on nuclear and mitochondrial genomes and consider organelle-specific therapeutic applications. Other goals are to understand structure-based traits facilitating EndoG interactions with MLL and the effects of peptides on fragile sites other than MLL.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1279: Exploiting the Human Peptidome for Novel Antimicrobial and Anticancer Agents
• Applicant Institution: Universität Ulm
• Project Heads: Professor Dr. Christof Gebhardt; Professorin Dr. Elisabeth Maria Wiesmüller