Reducing FASN expression sensitizes acute myeloid leukemia cells to differentiation therapy

• DOI: 10.1038/s41418-021-00768-1
• Publication Date: 2021-03-19T13:05:27Z
• Authors: Magali Humbert; Kristina Seiler; Severin Mosimann; Vreni Rentsch; Katyayani Sharma; Amit V. Pandey; Sharon L. McKenna; Mario P. Tschan
• Keywords: Differentiation Therapy

Abstract Fatty acid synthase (FASN) is the only human lipogenic enzyme available for de novo fatty synthesis and often highly expressed in cancer cells. We found that FASN mRNA levels were significantly higher acute myeloid leukemia (AML) patients than healthy granulocytes or CD34 + hematopoietic progenitors. Accordingly, decreased during all- trans retinoic (ATRA)-mediated granulocytic differentiation of promyelocytic (APL) cells, partially via autophagic degradation. Furthermore, our data suggest inhibition expression using RNAi (-)-epigallocatechin-3-gallate (EGCG) accelerated APL cell lines re-sensitized ATRA refractory non-APL AML reduction promoted translocation transcription factor EB (TFEB) to nucleus, paralleled by activation CLEAR network genes lysosomal biogenesis. Together, demonstrate combination with treatment facilitates cells may extend therapy