HOXA4 and B-cell chronic lymphocytic leukemia: Previous studies have identified genetic aberrations present at low frequencies in early-stage CLL that already enables prediction of patient prognosis,32,33 and the expansion of such subclones following therapeutic intervention.5 Our study has similarly identified DNA methylation at three DMRs, including HOXA4, that when measured in early disease are able to predict post-treatment survival, consistent with the expansion of subclones with altered methylation that were already present prior to exposure to therapy.