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High EVI1 expression in AML predicted a distinctly worse event-free survival and disease-free survival following multivariate analysis.
59,60) By employing next-generation sequencing and high-resolution chromosome conformation capture sequencing, Groschel et al (59) have mapped a 9-kb EVI1 -promoter-contact fragment within the 18-kb commonly translocated segment in AML and MDS patients with inv(3)/t(3;3).
By using a completely different approach, namely, bacterial artificial chromosome transgenic mouse model recapitulating the inv(3), Yamazaki et al60 have shown that the transgenic mice only developed leukemias when EVI1 was ectopically activated by G2DHE, but this did not happen in mice missing GATA2 enhancer, further corroborating the findings by Groschel and associates.
At the experimental level, Zhang et al (61) have showed that blocking of EVI1 DNA binding by pyrrole-imidazole polyamide 1 completely blocked EVI1 -responsive reporter activity, and the growth of a leukemic cell line bearing overexpressed EVI1 was also inhibited.
In summary, based on the aforementioned well-designed functional genomic studies, (59) as well as the use of transgenic mice model recapitulating the inv(3) allele, (60) it is clear that the inv(3)/t(3;3) results in reallocation of G2DHE to the proximity of EVI1, thus leading to the ectopic activation of EVI1 rather than the previously thought RPN1-EVI1 fusion transcript.
Activation of EVI1 gene expression in human acute myelogenous leukemias by translocations spanning 300-400 kilobases on chromosome band 3q26.
Repression of RUNX1 activity by EVI1: a new role of EVI1 in leukemogenesis.
Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well as in myeloid leukemia and produces a new member of the PR domain family.
Regulation of the expression of the oncogene EVI1 through the use of alternative mRNA 50ends.
Quantitative comparison of the expression of EVI1 and its presumptive antagonist, MDS1/EVI1, in patients with myeloid leukemia.
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- Evgraf Fedorovich Krendovskii
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- Evgrafov, Aleksei
- Evgrafov, Aleksei Romanovich
- Evgrafov, Georgii
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