A Remote GATA2 Hematopoietic Enhancer Drives Leukemogenesis in inv(3)(q21;q26) by Activating EVI1 Expression
Copyright policy )A Remote GATA2 Hematopoietic Enhancer Drives Leukemogenesis in inv(3)(q21;q26) by Activating EVI1 Expression
Chromosomal inversion between 3q21 and 3q26 results in high-risk acute myeloid leukemia (AML). In this study, we identified a mechanism whereby a GATA2 distal hematopoietic enhancer (G2DHE or -77-kb enhancer) is brought into close proximity to the EVI1 gene in inv(3)(q21;q26) inversions, leading to leukemogenesis. We examined the contribution of G2DHE to leukemogenesis by creating a bacterial artificial chromosome (BAC) transgenic model that recapitulates the inv(3)(q21;q26) allele. Transgenic mice harboring a linked BAC developed leukemia accompanied by EVI1 overexpression-neoplasia that was not detected in mice bearing the same transgene but that was missing the GATA2 enhancer. These results establish the mechanistic basis underlying the pathogenesis of a severe form of leukemia through aberrant expression of the EVI1 proto-oncogene.
- University of Michigan–Flint United States
- Tohoku University Japan
- University of Michigan Medical School United States
- University of Wisconsin School of Medicine and Public Health United States
- University of Wisconsin–Madison United States
Cancer Research, Base Sequence, Mice, Transgenic, Cell Biology, Transfection, Proto-Oncogene Mas, MDS1 and EVI1 Complex Locus Protein, Translocation, Genetic, Hematopoiesis, DNA-Binding Proteins, GATA2 Transcription Factor, Leukemia, Myeloid, Acute, Mice, Oncology, Chromosome Inversion, Proto-Oncogenes, Animals, Humans, Chromosomes, Human, Pair 3, Transgenes, Transcription Factors
Cancer Research, Base Sequence, Mice, Transgenic, Cell Biology, Transfection, Proto-Oncogene Mas, MDS1 and EVI1 Complex Locus Protein, Translocation, Genetic, Hematopoiesis, DNA-Binding Proteins, GATA2 Transcription Factor, Leukemia, Myeloid, Acute, Mice, Oncology, Chromosome Inversion, Proto-Oncogenes, Animals, Humans, Chromosomes, Human, Pair 3, Transgenes, Transcription Factors
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