CRISPR/Cas9-mediated KMT2A-rearrangements for the development of leukaemia mouse models

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KMT2A-chromosomal rearrangements are associated with the onset of acute leukaemia. Here, we present our data about CRISPR/Cas9-mediated chromosomal translocations. We either created t(4;11) or t(6;11) chromosomal translocations in umbilical cord blood (UCB) hematopoietic stem and progenitor cells which were transplanted into NSG mice. Many parameters regarding sgRNAs, transfection and culture conditions have been optimized in order to allow leukemic stem cell outgrowth. We did not observed any donor dependency as each UCB donor had the potential to generate CRISPR/Cas9-mediated t(4;11) and t(6;11) chromosomal translocations. In vivo experiments demonstrated rapid engraftment, oligoclonal expansion in bone marrow, liver and spleen. We can conclude that our optimized CRISPR/Cas9-system results in valuable mouse models that develop Leukemia within a few weeks and allows rapid research on different MLL-rearranged fusion proteins. Publication History Article published online: 10 May 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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