One possible explanation for the protective role of non-functional ITPA polymorphisms in relation to the relapse of ALL could be that the absence of functional ITPA activity can lead to the accumulation of non-canonical nucleotides that may cause DNA damage; such has also been demonstrated in an in vitro study on human HeLa cells with a knockdown ITPA gene [39]. The gene discussed is ITPA; the disease is acute lymphoblastic leukemia.