How Epigenetic Therapy Beats Adverse Genetics in Monosomy Karyotype AML

The study by Greve and colleagues, in this issue of Cancer Research, provides new molecular insights into the intriguing clinical activity DNA hypomethylating agents (HMA) patients with acute myeloid leukemia (AML) monosomal karyotypes. Patients AML adverse karyotypes are known to benefit from HMAs, but not cytarabine, a cytidine analog without HMA activity, specific mechanisms remain poorly understood. authors investigated mechanistic effects HMAs on gene reactivation context most common karyotypes, genetic deletion chromosome 7q 5q. They identified genes tumor-suppressive properties, an endogenous retrovirus cooperatively repressed hypermethylation, increased losses hemizygous chromosomal regions versus normal biallelic cell models. Treatment preferentially induced expression these levels similar those state. In addition CpG hypomethylation, decitabine treatment resulted histone acetylation open chromatin configuration specifically at loci. By using primary blood blasts isolated receiving patient-derived xenograft models established either or cytogenetics, colleagues both validated their findings patient samples demonstrated superior antileukemic compared chemotherapy cytarabine. These how epigenetic therapy beats genetics monosomy karyotype will therapeutic opportunities for difficult-to-treat group.See related article et al., p. 834