The main objective of this paper by Ando et al. was to explore the nature of association between the protein MEF/ELF4 and the nucleophosmin, NPM1, along with its implications with regards to leukemogenesis; the mutant version of the latter has been commonly associated with leukemia.
MEF/ELF4 is part of a family of transcriptional factors (ETS) responsible for numerous cellular functions, such as genomic stability, DNA repair, and most importantly, the regulation of cell proliferation, differentiation and cell death. In particular, MEF/ELF4 is expressed in hematopoietic cells in order to control their movement through the eukaryotic cell cycle, thus classifying it as a potential oncogene. Previous studies have demonstrated that the human HDM2 promoter is a target of the MEF transcriptional factor and the overexpression of MEF led to an increase in the Mdm2 protein (mice version of the human Hdm2), which in turn decreased the expression of the tumor-suppressor, p53, thereby augmenting transformation that may lead to leukemogenesis. Furthermore, the mutation commonly found in leukemia patients resulted in the delocalization of the NPM1 protein from the nucleolus to the …show more content…
Not only that, but this paper also includes a variety of techniques, some of which are unfamiliar, thus, providing me with the chance to learn. Moreover, the choice to include multiple techniques to prove one main point makes the author’s conclusions more convincing, as all of their assays worked in synergy. The findings of this paper may be able to suggest potential gene therapies for leukemia patients with normal karyotype but mutated NPM1 gene. Perhaps, siRNA targeted against the mutated gene or its restoration can inhibit NPM1’s aberrant expression in the cytoplasm. Since the mutation results in a nucleotide gain at the C termini, the truncation and subsequent re-folding of the protein may be able to restore its wild type
MEF/ELF4 is part of a family of transcriptional factors (ETS) responsible for numerous cellular functions, such as genomic stability, DNA repair, and most importantly, the regulation of cell proliferation, differentiation and cell death. In particular, MEF/ELF4 is expressed in hematopoietic cells in order to control their movement through the eukaryotic cell cycle, thus classifying it as a potential oncogene. Previous studies have demonstrated that the human HDM2 promoter is a target of the MEF transcriptional factor and the overexpression of MEF led to an increase in the Mdm2 protein (mice version of the human Hdm2), which in turn decreased the expression of the tumor-suppressor, p53, thereby augmenting transformation that may lead to leukemogenesis. Furthermore, the mutation commonly found in leukemia patients resulted in the delocalization of the NPM1 protein from the nucleolus to the …show more content…
Not only that, but this paper also includes a variety of techniques, some of which are unfamiliar, thus, providing me with the chance to learn. Moreover, the choice to include multiple techniques to prove one main point makes the author’s conclusions more convincing, as all of their assays worked in synergy. The findings of this paper may be able to suggest potential gene therapies for leukemia patients with normal karyotype but mutated NPM1 gene. Perhaps, siRNA targeted against the mutated gene or its restoration can inhibit NPM1’s aberrant expression in the cytoplasm. Since the mutation results in a nucleotide gain at the C termini, the truncation and subsequent re-folding of the protein may be able to restore its wild type