In AML, Convergent Epigenetic Evolution Drives Relapse

For patients with relapsed acute myeloid leukemia (AML), convergent epigenetic evolution can arise following induction chemotherapy treatment, according to Armon Azizi, MD-candidate, and colleagues who evaluated previously published research on AML relapse. For a study published in bioRxiv, they observed that 40% of relapses occur without changes in driver mutations, indicating that in a large proportion of cases of AML, relapse is driven by non-genetic mechanisms. Using 26 matched diagnosis-relapse samples with ATACseq, the researchers categorized epigenetic patterns of AML relapse, identifying a relapse-specific chromatin accessibility signature for mutationally stable AML. This suggests that at relapse independent of mutational changes, AML undergoes epigenetic evolution. “Analysis of leukemia stem cell (LSC) chromatin changes at relapse indicated that this leukemic compartment underwent significantly less epigenetic evolution than non- LSCs, while epigenetic changes in non-LSCs reflected overall evolution of the bulk leukemia,” the study authors wrote. In relapsed AML, they noted convergent epigenetic evolution. At relapse relative to diagnosis, they observed that distinct mitochondrially defined clones exhibit more similar chromatin accessibility.