NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap(4)A) and Down-Regulates Immune Response and Cancer Promotion Genes

Marriott, Andrew S.; Vasieva, Olga; Fang, Yongxiang; Copeland, Nikki A.; McLennan, Alexander G.; Jones, Nigel J.

Together, these data suggest reinforcement of elements of the adaptive immune response by elevated Ap 4 A. As far as KBM-7 cells are concerned, this may indicate that Ap 4 A is promoting their differentiation from a blast-like phenotype to a more mature stage [67] . There are some apparent exceptions, such as the down-regulation of the recombination activating genes RAG1 and RAG2 (down 4.4-and 107-fold respectively). The RAG proteins catalyze VDJ recombination and are essential for the generation of mature, functional T and B cells [68] . These genes are moderately expressed in KBM-7 cells and can be highly expressed in other blast-phase CML-derived cell lines, e.g. NALM-1 [69] . However, their relevance to immune function is in lymphocytes, in which their expression is normally confined, and in that context they may not be down-regulated by high Ap 4 A.