ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/beta-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

Automated summary

Acyl-CoA synthetase long chain family member 5 (ACSL5) is involved in activating long chain fatty acids and has been found to be dysregulated in certain cancers, including glioma and colon cancers. However, its role in acute myeloid leukemia (AML) is not well understood. This study demonstrates that ACSL5 is upregulated in bone marrow cells from AML patients and can serve as an independent prognostic predictor for their overall survival. Inhibition of ACSL5 suppresses AML cell growth through the Wnt/beta-catenin pathway and a combination of ACSL inhibitor and BCL-2 inhibitor shows promise for AML treatment.