title: High Expression of CPT1A Predicts Adverse Outcomes: A Potential Therapeutic Target for Acute Myeloid Leukemia.
abstract: Carnitine palmitoyl transferase 1A (CPT1A) protein catalyzes the rate-limiting step of Fatty-acid oxidation (FAO) pathway, which can promote cell proliferation and suppress apoptosis. Targeting CPT1A has shown remarkable anti-leukemia activity. But, its prognostic value remains unclear in Acute Myeloid Leukemia (AML). In two independent cohorts of cytogenetically normal AML (CN-AML) patients, compared to low expression of CPT1A (CPT1Alow), high expression of CPT1A (CPT1Ahigh) was significantly associated with adverse outcomes, which was also shown in European Leukemia Network (ELN) Intermediate-I category. Multivariable analyses adjusting for known factors confirmed CPT1Ahighas a high risk factor. Significant associations between CPT1Ahighand adverse outcomes were further validated whether for all AML patients (OS: P=0.008; EFS: P=0.002, n=334, no M3) or for National Comprehensive Cancer Network (NCCN) Intermediate-Risk subgroup (OS: P=0.021, EFS: P=0.024, n=173). Multiple omics analysis revealed aberrant alterations of genomics and epigenetics were significantly associated with CPT1A expression, including up- and down-regulation of oncogenes and tumor suppressor, activation and inhibition of leukemic (AML, CML) and immune activation pathways, hypermethylation enrichments on CpG island and gene promoter regions. Combined with the previously reported anti-leukemia activity of CPT1A's inhibitor, our results proved CPT1A as a potential prognosticator and therapeutic target for AML.
authors.affiliation: Key Laboratory of Biomedical Engineering and Translational Medicine (Chinese PLA General Hospital), Ministry of Industry and Information Technology, Beijing, China; Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Nuclear Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Fu
authors.affiliation: Key Laboratory of Biomedical Engineering and Translational Medicine (Chinese PLA General Hospital), Ministry of Industry and Information Technology, Beijing, China.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Key Laboratory of Biomedical Engineering and Translational Medicine (Chinese PLA General Hospital), Ministry of Industry and Information Technology, Beijing, China.
authors.forename: Kunlun
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address: fulin022@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Key Laboratory of Biomedical Engineering and Translational Medicine (Chinese PLA General Hospital), Ministry of Industry and Information Technology, Beijing, China; Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing, China. Electronic address: wangwd301@126.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics*; D016000:Cluster Analysis; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011379:Prognosis; D059467:Transcriptome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs; C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase
keywords: AML; Biomarker; CPT1A; Expression; Prognosis