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000292145 1001_ $$0P:(DE-He78)ff4024f7bc236e7897d9c18ee19c451f$$aWeichenhan, Dieter$$b0$$eFirst author$$udkfz
000292145 245__ $$aAltered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13).
000292145 260__ $$aWashington, DC$$bAmerican Society of Hematology$$c2024
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000292145 500__ $$a#EA:B370#EA:B087#LA:B370#LA:B340# / 2024 Oct 8;8(19):5100-5111
000292145 520__ $$aAcute myeloid leukemia (AML) with the t(7;12)(q36;p13) translocation occurs only in very young children and has a poor clinical outcome. The expected oncofusion between breakpoint partners (MNX1 and ETV6) has only been reported in a subset of cases. However, a universal feature is the strong transcript and protein expression of MNX1, a homeobox transcription factor that is normally not expressed in hematopoietic cells. Here, we map the translocation breakpoints on chromosomes 7 and 12 in affected patients to a region proximal to MNX1 and either introns 1 or 2 of ETV6. The frequency of MNX1 overexpression in pediatric AML (n=1556, own and published data) is 2.4% and occurs predominantly in t(7;12)(q36;p13) AML. Chromatin interaction assays in a t(7;12)(q36;p13) iPSC cell line model unravel an enhancer-hijacking event that explains MNX1 overexpression in hematopoietic cells. Our data suggest that enhancer-hijacking may be a more widespread consequence of translocations where no oncofusion product was identified, including e.g. t(1;3) or t(4;12) AML.
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000292145 7001_ $$0P:(DE-He78)72478c70ea4e197e956747e5cefcbea7$$aRiedel, Anna$$b1$$eFirst author$$udkfz
000292145 7001_ $$0P:(DE-He78)690891e88caacd9f6327522d7d167149$$aSollier, Etienne$$b2$$eFirst author$$udkfz
000292145 7001_ $$0P:(DE-He78)cd8295952c28dc5b483b5ba9386a5669$$aToprak, Umut$$b3$$eFirst author
000292145 7001_ $$0P:(DE-He78)198a73f54b40192a2fdc2bf53ba7ca27$$aHey, Joschka$$b4$$udkfz
000292145 7001_ $$0P:(DE-He78)75efcd61c13c2fbe457cdf3454ef486c$$aBreuer, Kersten$$b5$$udkfz
000292145 7001_ $$0P:(DE-He78)fd7de20653a8cbc8aee25717fa667280$$aWierzbinska, Justyna Anna$$b6
000292145 7001_ $$0P:(DE-He78)fecdc89b0d86f5eb9d4e169175ebc6cb$$aTouzart, Aurore$$b7
000292145 7001_ $$0P:(DE-He78)ff1677c63392be9b31a1c8d23db7c9dc$$aLutsik, Pavlo$$b8$$udkfz
000292145 7001_ $$0P:(DE-He78)cfd12c2b002e4edb674103723a470712$$aBähr, Marion$$b9$$udkfz
000292145 7001_ $$aÖstlund, Anders$$b10
000292145 7001_ $$aNilsson, Tina$$b11
000292145 7001_ $$aJacobsson, Susanna$$b12
000292145 7001_ $$00000-0003-4635-021X$$aWaraky, Ahmed$$b13
000292145 7001_ $$aBehrens, Yvonne Lisa$$b14
000292145 7001_ $$aGöhring, Gudrun$$b15
000292145 7001_ $$00000-0001-5256-1270$$aSchlegelberger, Brigitte$$b16
000292145 7001_ $$00000-0003-3590-2103$$aSteinek, Clemens$$b17
000292145 7001_ $$00000-0003-1218-2107$$aHarz, Hartmann$$b18
000292145 7001_ $$00000-0002-5086-6449$$aLeonhardt, Heinrich$$b19
000292145 7001_ $$aDolnik, Anna$$b20
000292145 7001_ $$00000-0002-7027-4483$$aReinhardt, Dirk$$b21
000292145 7001_ $$aBullinger, Lars$$b22
000292145 7001_ $$00000-0001-9274-360X$$aPalmqvist, Lars$$b23
000292145 7001_ $$0P:(DE-He78)c403a040c97f91902a7d31b93859f9fc$$aLipka, Daniel$$b24$$eLast author$$udkfz
000292145 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b25$$eLast author$$udkfz
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