Altered enhancer-promoter interaction leads to<i>MNX1</i>expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13)
ETV6oncofusion gene..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 03. Nov. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Weichenhan, Dieter [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
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| doi: |
10.1101/2023.09.13.557546 |
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| PPN (Katalog-ID): |
XBI040873072 |
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| 100 | 1 | |a Weichenhan, Dieter |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Altered enhancer-promoter interaction leads to<i>MNX1</i>expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13) |
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| 520 | |a 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 (MNX1andETV6) 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 toMNX1and either introns 1 or 2 ofETV6. The frequency ofMNX1overexpression 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 explainsMNX1overexpression in hematopoietic cells. Our data suggest that enhancer-hijacking is a more common and overlooked mechanism for structural rearrangement-mediated gene activation in AML.Key points <jats:list list-type="bullet">Expression analysis of over 1500 pediatric AML samples demonstratesMNX1expression as a universal feature of t(7;12)(q36;p13) AML as well as in rare cases without t(7;12)(q36;p13)MNX1is activated by an enhancer-hijacking event in t(7;12)(q36;p13) AML and not, as previously postulated, by the creation of aMNX1::ETV6oncofusion gene. | ||
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| 700 | 1 | |a Sollier, Etienne |4 aut | |
| 700 | 1 | |a Toprak, Umut H. |4 aut | |
| 700 | 1 | |a Hey, Joschka |4 aut | |
| 700 | 1 | |a Breuer, Kersten |4 aut | |
| 700 | 1 | |a Wierzbinska, Justyna A. |4 aut | |
| 700 | 1 | |a Touzart, Aurore |4 aut | |
| 700 | 1 | |a Lutsik, Pavlo |0 (orcid)0000-0001-9383-8555 |4 aut | |
| 700 | 1 | |a Bähr, Marion |4 aut | |
| 700 | 1 | |a Östlund, Anders |4 aut | |
| 700 | 1 | |a Nilsson, Tina |4 aut | |
| 700 | 1 | |a Jacobsson, Susanna |4 aut | |
| 700 | 1 | |a Edler, Marcel |4 aut | |
| 700 | 1 | |a Waraky, Ahmed |0 (orcid)0000-0003-4635-021X |4 aut | |
| 700 | 1 | |a Behrens, Yvonne Lisa |4 aut | |
| 700 | 1 | |a Göhring, Gudrun |4 aut | |
| 700 | 1 | |a Schlegelberger, Brigitte |4 aut | |
| 700 | 1 | |a Steinek, Clemens |4 aut | |
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