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Curcumin as an epigenetic therapeutic agent in myelodysplastic syndromes (MDS)

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 presenc...

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Main Authors: Xie, Xiaoqing (Author) , Frank, Daria (Author) , Patnana, Pradeep Kumar (Author) , Schütte, Judith (Author) , Al-Matary, Yahya Saleh Ahmed (Author) , Liu, Longlong (Author) , Wei, Lanying (Author) , Dugas, Martin (Author) , Varghese, Julian (Author) , Nimmagadda, Subbaiah Chary (Author) , Khandanpour, Cyrus (Author)
Format: Article (Journal)
Language:English
Published: 2022
In: International journal of molecular sciences
Year: 2022, Volume: 23, Issue: 1, Pages: 1-13
ISSN:1422-0067
DOI:10.3390/ijms23010411
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/ijms23010411
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1422-0067/23/1/411
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Author Notes:Xiaoqing Xie, Daria Frank, Pradeep Kumar Patnana, Judith Schütte, Yahya Al-Matary, Longlong Liu, Lanying Wei, Martin Dugas, Julian Varghese, Subbaiah Chary Nimmagadda and Cyrus Khandanpour
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Summary: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.
Item Description:Published: 30 December 2021
Gesehen am 21.09.2022
Physical Description:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms23010411

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