Moreover, A-to-I editing of both the MDM2 regulatory microRNA and its binding site within the 3' UTR region stabilizes MDM2 transcripts, thereby enhancing blast crisis progenitor propagation.
Two functional single nucleotide polymorphisms (SNPs), p53 R72P and MDM2 SNP309, are associated with alternation of p53 activity, however the association regarding CML susceptibility and BP transformation under imatinib treatment is unclear.
We conclude that HDM-2 inhibition with MI-219 effectively induces p53-dependent apoptosis in most blast crisis CML cells, with or without BCR-ABL mutation(s).
Expression of MDM2, the negative regulator of p53, was upregulated in a tyrosine kinase-dependent manner in growth factor-independent BCR/ABL-expressing cells, and in accelerated phase and blast crisis CML samples.