Daria Frank, Pradeep Kumar Patnana, Jan Vorwerk, Lianghao Mao, Lavanya Mokada Gopal, Noelle Jung, Thorben Hennig, Leo Ruhnke, Joris Maximillian Frenz, Maithreyan Kuppusamy, Robert J Autry, Lanying Wei, Kaiyan Sun, Helal Ahmed, Axel Künstner, Hauke Busch, Heiko Müller, Stephan Hutter, Gregor Hoermann, Longlong Liu, Xiaoqing Xie, Yahya Al-Matary, Subbaiah Chary Nimmagadda, Fiorella Charles Cano, Michael Heuser, Felicitas R Thol, Gudrun Göhring, Doris Steinemann, Jürgen Thomale, Theo Leitner, Anja Fischer, Roland Rad, Christoph Röllig, Heidi Altmann, Desiree Kunadt, Wolfgang E Berdel, Jana Hüve, Felix Neumann, Jürgen Klingauf, Virginie Calderon, Bertram Opalka, Ulrich Dührsen, Frank Rosenbauer, Martin Dugas, Julian Varghese, H Christian H Reinhardt, Nikolas von Bubnoff, Tarik Möröy, Georg Lenz, Aarif M N Batcha, Marianna Giorgi, Murugan Selvam, Eunice S Wang, Shannon K McWeeney, Jeffrey W Tyner, Friedrich Stölzel, Matthias Mann, Ashok Kumar Jayavelu, Cyrus Khandanpour
Growth Factor Independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of haematopoiesis. GFI1-36N is a germline variant causing a change of serine (S) to asparagine (N) at position 36. We previously reported that the GFI1-36N allele has a prevalence of 10-15% among patients with acute myeloid leukemia (AML) and 5-7% among healthy Caucasians and promotes the development of this disease. Using a multi-omics approach, we show here that GFI1-36N expression is associated with increased frequencies of chromosomal aberrations, mutational burden and mutational signatures in both murine and human AML and impedes homologous recombination-directed (HR) DNA repair in leukemic cells...
September 26, 2023: Blood