Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13).
Blood Advances article with contributions from the Leonhardt lab
09.08.2024
Weichenhan D, Riedel A, Sollier E, Toprak UH, Hey J, Breuer KH, Wierzbinska JA, Touzart A, Lutsik P, Bähr M, Östlund A, Nilsson T, Jacobsson S, Waraky A, Behrens YL, Göhring G, Schlegelberger B, Steinek C, Harz H,Leonhardt H, Dolnik A, Reinhardt D, Bullinger L, Palmqvist L, Lipka DB and Plass C (2024 Aug 9 ). Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13). Blood Adv., (Epub ahead of print). 10.1182/bloodadvances.2023012161
Abstract cited directly from the article:
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.