Autophagy-mediated degradation of Fatty Acid Synthase (FASN) facilitates ATRA-induced granulocytic differentiation of acute myeloid leukemia (AML) cells

Acute myeloid leukemia (AML) is a blood cancer characterized by a block in differentiation and increased survival of the resulting AML blast cells. While standard chemotherapy for AML cures only 30% of patients, differentiation-inducing therapy using all-trans retinoic acid (ATRA) in combination with arsenic trioxide achieves 90% cure rates in acute promyelocytic leukemia (APL). A better understanding of the molecular mechanisms underlying ATRA therapy in APL may provide new perspectives in the treatment of additional AML subtypes. Fatty acid synthase (FASN) is the only human lipogenic enzyme available for de novo fatty acid synthesis. While FASN levels are very low in healthy adult tissues, it is often highly expressed in cancer cells, thus representing a potential therapeutic target. We found that FASN mRNA levels were significantly higher in AML patients than in healthy granulocytes or CD34+ hematopoietic progenitors in two AML cohorts (n=68, n=203) (p