Reducing FASN expression sensitizes acute myeloid leukemia cells to differentiation therapy.

Humbert, Magali; Seiler, Kristina; Mosimann, Severin; Rentsch, Vreni; Sharma, Katyayani; Pandey, Amit V.; McKenna, Sharon L.; Tschan, Mario P. (2021). Reducing FASN expression sensitizes acute myeloid leukemia cells to differentiation therapy. (In Press). Cell death and differentiation Springer Nature 10.1038/s41418-021-00768-1

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

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Humbert, Magali; Seiler, Kristina; Sharma, Katyayani; Pandey, Amit Vikram and Tschan, Mario

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1350-9047

Publisher:

Springer Nature

Language:

English

Submitter:

Mario Tschan

Date Deposited:

20 May 2021 12:16

Last Modified:

20 May 2021 12:16

Publisher DOI:

10.1038/s41418-021-00768-1

PubMed ID:

33742137

BORIS DOI:

10.48350/155981

URI:

https://boris.unibe.ch/id/eprint/155981

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