Journal Article

DKFZ-2024-01633

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13).

Weichenhan, D. (First author)DKFZ* ; Riedel, A. (First author)DKFZ* ; Sollier, E. (First author)DKFZ* ; Toprak, U. (First author)DKFZ* ; Hey, J.DKFZ* ; Breuer, K.DKFZ* ; Wierzbinska, J. A.DKFZ* ; Touzart, A.DKFZ* ; Lutsik, P.DKFZ* ; Bähr, M.DKFZ* ; 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. (Last author)DKFZ* ; Plass, C. (Last author)DKFZ*

2024
American Society of Hematology Washington, DC

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Please use a persistent id in citations: doi:10.1182/bloodadvances.2023012161

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.

Note: #EA:B370#EA:B087#LA:B370#LA:B340# / 2024 Oct 8;8(19):5100-5111

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Contributing Institute(s):

1. Epigenomik (B370)
2. B087 Neuroblastom Genomik (B087)
3. Translationale Medizinische Onkologie (B340)
4. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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