Deletions within the locus of the large HECT E3 ubiquitin ligase HERC1 have been observed in acute lymphoblastic leukemia (ALL) and have been associated to an increased resistance to thiopurine antileukemic agents due to the control that HERC1 exerts on the stability of the DNA mismatch repair enzyme MSH2 [11]. The gene discussed is MSH2; the disease is acute lymphoblastic leukemia.