Loss of Y-chromosome in Acute Myeloid Leukemia drives tumor cell plasticity and drug resistance (A04)

• Subject Area: Hematology, Oncology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 533056198

Project A04 proposes that loss of KDM5D, a chromosome Y-specific histone H3 lysine-4 demethylase, associates with deficiencies in DNA repair and increases epigenetic and functional plasticity of human AML cells with mosaic loss of Y chromosome (mLOY). Using sc-multi omics approaches on engineered LOY iPSC/HSPC cells and primary patient samples as well as PDX mouse models A04 will analyze whether mLOY creates haploinsufficiency in epigenetic enzymes encoded on the Y chromosome, resulting in epigenomic heterogeneity of H3K4me3 and determine the impact of KDM5D/UTY/KDM6C loss on the functional plasticity of AML stem cells.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1709: Cellular Plasticity in Myeloid Malignancies: From Mechanisms to Therapies
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Professor Dr. Alwin Krämer; Professor Dr. Christoph Plass