The pressure to inactivate DNA damage checkpoint signaling is reflected by the fact that therapy-related AML more frequently harbor TP53 mutations than AML developing de novo111 and that clones harboring TP53 mutations are selected during malignant transformation of therapy-related AML.112 Similarly, CHK1 and CHK2 are strongly activated in MDS, but almost completely inactivated in MDR-AML cells.113. This evidence concerns the gene CHEK1 and acute myeloid leukemia.