Glucocorticoid resistance may be implicated in the emergence of ETV6/RUNX1- positive relapses

Although ETV6/RUNX1 (E/R)-positive ALL is generally associated with excellent treatment response, up to 20% of cases suffer a relapse. To gain insight into relapse mechanisms we analyzed genome-wide copy number aberrations in 18 matched diagnosis and relapse leukemias. Strikingly, we identified recurrent deletions of genes implicated in glucocorticoid (GC) mediated apoptosis affecting NR3C1 and BMF encoding the GC receptor and the Bcl2 modifying factor, respectively. BMF deletions were present in about 17% of children already at initial diagnosis and conserved at relapse, but were significantly less frequent (