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| Item Type: | Article |
|---|---|
| Title: | Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13) |
| Creators Name: | Weichenhan, D., Riedel, A., Sollier, E., Toprak, U.H., Hey, J., Breuer, K.H., Wierzbinska, J.A., Touzart, A., Lutsik, P., Bähr, M., Östlund, A., Nilsson, T., Jacobsson, S., Waraky, A., Behrens, Y.L., Göhring, G., Schlegelberger, B., Steinek, C., Harz, H., Leonhardt, H., Dolnik, A., Reinhardt, D., Bullinger, L., Palmqvist, L., Lipka, D.B. and Plass, C. |
| Abstract: | Acute myeloid leukemia (AML) with the t(7;12)(q36;p13) translocation occurs only in very young children and has a poor clinical outcome. The expected oncofusion between breakpoint partners (MNX1 and ETV6) has only been reported in a subset of cases. However, a universal feature is the strong transcript and protein expression of MNX1, a homeobox transcription factor that is normally not expressed in hematopoietic cells. Here, we map the translocation breakpoints on chromosomes 7 and 12 in affected patients to a region proximal to MNX1 and either introns 1 or 2 of ETV6. The frequency of MNX1 overexpression in pediatric AML (n=1556, own and published data) is 2.4% and occurs predominantly in t(7;12)(q36;p13) AML. Chromatin interaction assays in a t(7;12)(q36;p13) iPSC cell line model unravel an enhancer-hijacking event that explains MNX1 overexpression in hematopoietic cells. Our data suggest that enhancer-hijacking may be a more widespread consequence of translocations where no oncofusion product was identified, including e.g. t(1;3) or t(4;12) AML. |
| Keywords: | Acute Myeloid Leukemia, ETS Translocation Variant 6 Protein, Genetic Enhancer Elements, Genetic Promoter Regions, Genetic Translocation, Homeodomain Proteins, Leukemic Gene Expression Regulation, Pair 7 Human Chromosomes, Proto-Oncogene Proteins c-ets, Repressor Proteins, Transcription Factors |
| Source: | Blood Advances |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Volume: | 8 |
| Number: | 19 |
| Page Range: | 5100-5111 |
| Date: | 8 October 2024 |
| Official Publication: | https://doi.org/10.1182/bloodadvances.2023012161 |
| PubMed: | View item in PubMed |
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