TY - JOUR A1 - Wilhelm, Alexander A1 - Marschalek, Rolf T1 - The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(4;11) T2 - Oncogene N2 - Leukemia patients bearing the t(4;11)(q21;q23) translocations can be divided into two subgroups: those expressing both reciprocal fusion genes, and those that have only the MLL-AF4 fusion gene. Moreover, a recent study has demonstrated that patients expressing both fusion genes have a better outcome than patients that are expressing the MLL-AF4 fusion protein alone. All this may point to a clonal process where the reciprocal fusion gene AF4-MLL could be lost during disease progression, as this loss may select for a more aggressive type of leukemia. Therefore, we were interested in unraveling the decisive role of the AF4-MLL fusion protein at an early timepoint of disease development. We designed an experimental model system where the MLL-AF4 fusion protein was constitutively expressed, while an inducible AF4-MLL fusion gene was induced for only 48 h. Subsequently, we investigated genome-wide changes by RNA- and ATAC-Seq experiments at distinct timepoints. These analyses revealed that the expression of AF4-MLL for only 48 h was sufficient to significantly change the genomic landscape (transcription and chromatin) even on a longer time scale. Thus, we have to conclude that the AF4-MLL fusion protein works through a hit-and-run mechanism, probably necessary to set up pre-leukemic conditions, but being dispensable for later disease progression. KW - Cell biology KW - Genetics Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63476 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-634769 SN - 1476-5594 N1 - This work is funded by DFG grants Ma 1876/12-1 and Ma 1876/13-1, and grant 2018.070.1 and 2018.070.2 from the Wilhelm Sander Foundation. Open Access funding enabled and organized by Projekt DEAL. VL - 40 SP - 6093 EP - 6102 PB - Springer Nature CY - London ER -