We recently reported that induced expression of the dual-specificity kinase DYRK2 either by genetic loss of the Krüppel-like factor 4 (KLF4) or inhibition of the ubiquitin ligase SIAH2, which is involved in DYRK2 proteolysis, abrogates the self-renewal and survival of CML LSCs14. The gene discussed is KLF4; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.