These data indicate that MOZ-TIF2/BRPF1 complex upregulates HOX genes mediated by MOZ-dependent histone acetylation, leading to the development of leukemia.
In addition, ETV6-NCOA2leukemia shows a high frequency of heterozygous activating NOTCH1 mutations, which disrupt the heterodimerization or the PEST domains.
Although leukemia-derived fusion proteins such as MOZ-TIF2 promote self-renewal of leukemic stem cells, recent studies indicate that murine MOZ and MORF are important for proper development of hematopoietic and neurogenic progenitors, respectively, thereby highlighting the importance of epigenetic integrity in safeguarding stem cell identity.
This similarity is also apparent at the molecular genetic level, in-as-much as the MOZ gene in 8p11 is rearranged in both the translocation and the inversion; in t(8;16)-positive leukemia, a MOZ-CBP chimeric gene is generated, whereas inv(8) has been shown to generate a MOZ-TIF2 fusion gene.