CPT1B promotes acute myeloid leukemia progression via fatty acid oxidation-dependent metabolic reprogramming

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with limited treatment options, especially in cases of relapse or refractory disease. Metabolic reprogramming, particularly fatty acid oxidation (FAO), has emerged as a critical mechanism in AML progression. Carnitine palmitoyltransferase 1B (CPT1B), a rate-limiting enzyme in mitochondrial FAO, is highly expressed in metabolically active tissues, yet its role in AML remains poorly defined.

CPT1B expression was analyzed using TCGA datasets, patient samples, and AML cell lines. Functional studies employed CPT1B knockdown (shRNA) and overexpression (lentiviral) models in AML cell lines (THP-1, KG-1, HL-60, HEL). In vitro and in vivo effects were assessed via CCK-8, flow cytometry, western blot, ELISA, and xenograft models in immunodeficient mice. The FAO inhibitor Etomoxir was used to evaluate metabolic dependency.

CPT1B was significantly overexpressed in AML tissues and cell lines compared to normal controls and correlated with poorer overall survival. CPT1B knockdown reduced proliferation, induced G0/G1 cell cycle arrest, and promoted apoptosis in AML cells. CPT1B silencing inhibited tumor growth and dissemination in vivo. Conversely, CPT1B overexpression enhanced FAO activity, increased lipid droplet accumulation, and upregulated PPARA, CPT1A, and ACOX1 expression. Treatment with Etomoxir reversed these effects, restoring apoptosis and inhibiting CPT1B-driven proliferation both in vitro and in mouse models.

CPT1B acts as a key metabolic driver of AML progression through FAO-dependent lipid metabolic reprogramming. Its inhibition suppresses leukemic growth and improves survival outcomes, identifying the CPT1B-FAO axis as a promising therapeutic target and prognostic biomarker in AML.