Clonal medicine targeting DNA damage response eradicates leukemia

Clonal diversity plays a key role in poor therapeutic outcomes in acute myeloid leukemia (AML) and myeloproliferative neoplasm (MPN) patients. Therefore, targeting all clones is required to eradicate these diseases. To achieve this goal, we integrated genetic clonal landscape of individual patient samples with the response to DNA double-strand break repair (DSBR) inhibitors to track individual clones’ sensitivity to these drugs. We decided to target DSBR pathways because AML and MPN accumulate high numbers of DSBs, the most lethal of all DNA lesions resulting from altered metabolism. Thus, survival and proliferation of AML and MPN cells depend on DSBR mechanisms which represent a promising targetable vulnerability