Curcumin as an Epigenetic Therapeutic Agent in Myelodysplastic Syndromes (MDS)

International Journal of Molecular Sciences

Yahya Al-Matary¹  Pradeep Kumar Patnana²  Daria Frank²  Lanying Wei²  Xiaoqing Xie²  Subbaiah Chary Nimmagadda²  Judith Schütte²  Cyrus Khandanpour²  Longlong Liu²  Martin Dugas³  Julian Varghese⁴ 

[1] Department of Dermatology, University Hospital Essen, 45147 Essen, Germany;Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, 48149 Münster, Germany;Institute of Medical Informatics, Heidelberg University Hospital, 69117 Heidelberg, Germany;Institute of Medical Informatics, University Münster, 48149 Münster, Germany;

关键词: GFI1;    acute myeloid leukaemia;    histone acetyltransferase inhibitor;    curcumin;   

DOI  :  10.3390/ijms23010411

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown