title: Inhibition of pentose phosphate pathway suppresses acute myelogenous leukemia.
abstract: Pentose phosphate pathway (PPP) is a metabolic pathway that generates NADPH and pentose. PPP genes have been reported to be primarily or secondarily upregulated in many cancers. We aimed to study the general alteration of PPP in acute myelogenous leukemia (AML). We performed data mining and analysis of the Cancer Genome Atlas (TCGA) AML dataset for genetic alteration of the PPP gene set. In vitro studies including proliferation, migration, and invasion assays, together with metabolite consumption and oxidation assays, were performed. PPP genes were upregulated in 61 % of patients with AML. The majority of altered cases were expression changes measured by RNA sequencing. Expressions of critical PPP genes such as G6PD, PFKL, PFKP, and PGLS were consistently upregulated in all altered cases. Altered PPP is not associated with survival or disease relapse. PPP inhibition using 6-aminonicotinamide (6AN) increases glucose oxidative metabolism in AML. 6AN decreased the glucose oxidation and increased fatty acid oxidation. Here, we showed that PPP inhibition increased glucose oxidative metabolism in AML. PPP inhibition suppressed growth, migration, and invasion of AML, but not colony formation. PPP plays an important role in AML. Our results could contribute to the development of novel targeted treatment.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Ji
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Huamei
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Bolin
authors.initials: B
authors.lastname: Wan
authors.affiliation: Department of Hematology, Jiangxi Academy of Medical Science, Nanchang, 330006, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. rbhuanghematol@163.com.
authors.forename: Ruibin
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. gachenhematol@163.com.
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
mesh_terms: D015120:6-Aminonicotinamide / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D014644:Genetic Variation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D010084:Oxidation-Reduction / Q000187:drug effects; D010427:Pentose Phosphate Pathway; D011379:Prognosis
chemical_list: D015120:6-Aminonicotinamide; D005947:Glucose
keywords: 6-Aminonicotinamide; Acute myelogenous leukemia; Pentose phosphate pathway