TY - JOUR AB - Growth Factor Independence 1 (GFI1) is a transcription factor with an important role in the regulation of development of myeloid and lymphoid cell lineages and was implicated in the development of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Reduced expression of GFI1 or presence of the GFI1-36N (serine replaced with asparagine) variant leads to epigenetic changes in human and murine AML blasts and accelerated the development of leukaemia in a murine model of human MDS and AML. We and other groups previously showed that the GFI1-36N allele or reduced expression of GFI1 in human AML blasts is associated with an inferior prognosis. Using GFI1-36S, -36N -KD, NUP98-HOXD13-tg mice and curcumin (a natural histone acetyltransferase inhibitor (HATi)), we now demonstrate that expansion of GFI1-36N or –KD, NUP98-HODXD13 leukaemic cells can be delayed. Curcumin treatment significantly reduced AML progression in GFI1-36N or -KD mice and prolonged AML-free survival. Of note, curcumin treatment had no effect in GFI1-36S, NUP98-HODXD13 expressing mice. On a molecular level, curcumin treatment negatively affected open chromatin structure in the GFI1-36N or -KD haematopoietic cells but not GFI1-36S cells. Taken together, our study thus identified a therapeutic role for curcumin treatment in the treatment of AML patients (homo or heterozygous for GFI1-36N or reduced GFI1 expression) and possibly improved therapy outcome. AU - Xie, Xiaoqing AU - Frank, Daria AU - Patnana, Pradeep Kumar AU - Schütte, Judith AU - Al-Matary, Yahya Saleh Ahmed AU - Liu, Longlong AU - Wei, Lanying AU - Dugas, Martin AU - Varghese, Julian AU - Nimmagadda, Subbaiah Chary AU - Khandanpour, Cyrus DA - 2021-12-30 DO - 10.17879/84069414101 KW - GFI1 KW - acute myeloid leukaemia KW - histone acetyltransferase inhibitor KW - curcumin LA - eng N1 - International Journal of Molecular Science 23 (2022) 1, 411, 1-13 N1 - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster). N1 - Förderer: Deutsche José Carreras Leukämie-Stiftung / Projektnummer: DJCLS 17R/2018 N1 - Funding organisation: Deutsche José Carreras Leukämie-Stiftung / Project number: DJCLS 17R/2018 PY - 2021-12-30 TI - Curcumin as an Epigenetic Therapeutic Agent in Myelodysplastic Syndromes (MDS) UR - https://nbn-resolving.org/urn:nbn:de:hbz:6-74069413345 Y2 - 2024-11-22T04:47:35 ER -