Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13)
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 break point partners (motor neuron and pancreas homeobox 1 [MNX1] and ETS variant transcription factor 6 [ETV6]) has only been repo...
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
October 8, 2024
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| In: |
Blood advances
Year: 2024, Jahrgang: 8, Heft: 19, Pages: 5100-5111 |
| ISSN: | 2473-9537 |
| DOI: | 10.1182/bloodadvances.2023012161 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/bloodadvances.2023012161 Verlag, lizenzpflichtig, Volltext: https://ashpublications.org/bloodadvances/article/8/19/5100/517303/Altered-enhancer-promoter-interaction-leads-to 
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| Verfasserangaben: | Dieter Weichenhan, Anna Riedel, Etienne Sollier, Umut H. Toprak, Joschka Hey, Kersten Breuer, Justyna A. Wierzbinska, Aurore Touzart, Pavlo Lutsik, Marion Bähr, Anders Östlund, Tina Nilsson, Susanna Jacobsson, Marcel Edler, Ahmed Waraky, Yvonne Lisa Behrens, Gudrun Göhring, Brigitte Schlegelberger, Clemens Steinek, Hartmann Harz, Heinrich Leonhardt, Anna Dolnik, Dirk Reinhardt, Lars Bullinger, Lars Palmqvist, Daniel B. Lipka, and Christoph Plass |
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| 245 | 1 | 0 | |a Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13) |c Dieter Weichenhan, Anna Riedel, Etienne Sollier, Umut H. Toprak, Joschka Hey, Kersten Breuer, Justyna A. Wierzbinska, Aurore Touzart, Pavlo Lutsik, Marion Bähr, Anders Östlund, Tina Nilsson, Susanna Jacobsson, Marcel Edler, Ahmed Waraky, Yvonne Lisa Behrens, Gudrun Göhring, Brigitte Schlegelberger, Clemens Steinek, Hartmann Harz, Heinrich Leonhardt, Anna Dolnik, Dirk Reinhardt, Lars Bullinger, Lars Palmqvist, Daniel B. Lipka, and Christoph Plass |
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| 520 | |a 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 break point partners (motor neuron and pancreas homeobox 1 [MNX1] and ETS variant transcription factor 6 [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 break points 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 is 2.4% and occurs predominantly in t(7;12)(q36;p13) AML. Chromatin interaction assays in a t(7;12)(q36;p13) induced pluripotent stem 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 in which no oncofusion product was identified, including t(1;3) or t(4;12) AML. | ||
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