Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia
Abstract Acute lymphoblastic leukemia (ALL) and its treatment continue to pose substantial risks. To understand ALL more deeply, the metabolome in fasting plasma of 27 ALL patients before and after high-dose methotrexate therapies (consolidation therapy) including methotrexate and 6-mercaptopurine (...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Cancer & Metabolism |
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| Online Access: | https://doi.org/10.1186/s40170-023-00302-6 |
| _version_ | 1811175743542001664 |
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| author | Jinqiu Fu Aijun Zhang Qinqin Liu Dong Li Xiaoming Wang Libo Si |
| author_facet | Jinqiu Fu Aijun Zhang Qinqin Liu Dong Li Xiaoming Wang Libo Si |
| author_sort | Jinqiu Fu |
| collection | DOAJ |
| description | Abstract Acute lymphoblastic leukemia (ALL) and its treatment continue to pose substantial risks. To understand ALL more deeply, the metabolome in fasting plasma of 27 ALL patients before and after high-dose methotrexate therapies (consolidation therapy) including methotrexate and 6-mercaptopurine (6-MP) was investigated. Plasma metabolites were analyzed using liquid chromatography–tandem mass spectrometry (LC–MS). Orthogonal projections to latent structures discriminant analysis and significance analysis of microarrays were used to evaluate the metabolic changes. Pathway enrichment and co-expression network analyses were performed to identify clusters of molecules, and 2826 metabolites were identified. Among them, 38 metabolites were identified by univariate analysis, and 7 metabolites that were altered by conditioning therapy were identified by multivariate analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for pathway enrichment analysis. Among the enriched KEGG pathways, the 3 significantly altered metabolic pathways were pyrimidine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. In addition, L-phenylalanine was significantly correlated with blood urea nitrogen (BUN), and palmitoylcarnitine was correlated with aspartate aminotransferase (AST). In summary, consolidation therapy significantly affected pyrimidine- and phenylalanine-associated metabolic pathways in pediatric ALL patients. These findings may provide an insight into the role of metabolic profiling in consolidation treatment and as a potential for pediatric ALL patients. |
| first_indexed | 2024-04-10T19:40:49Z |
| format | Article |
| id | doaj.art-4ff0739fac8e4b9cb6bea4230659a76f |
| institution | Directory Open Access Journal |
| issn | 2049-3002 |
| language | English |
| last_indexed | 2024-04-10T19:40:49Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer & Metabolism |
| spelling | doaj.art-4ff0739fac8e4b9cb6bea4230659a76f2023-01-29T12:19:58ZengBMCCancer & Metabolism2049-30022023-01-0111111010.1186/s40170-023-00302-6Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemiaJinqiu Fu0Aijun Zhang1Qinqin Liu2Dong Li3Xiaoming Wang4Libo Si5Department of Pediatrics, Qilu Hospital of Shandong UniversityDepartment of Pediatrics, Qilu Hospital of Shandong UniversityDepartment of Pediatrics, Qilu Hospital of Shandong UniversityDepartment of Pediatrics, Qilu Hospital of Shandong UniversityDepartment of Pediatrics, Qilu Hospital of Shandong UniversityDepartment of Thoracic Surgery, Qilu Hospital of Shandong UniversityAbstract Acute lymphoblastic leukemia (ALL) and its treatment continue to pose substantial risks. To understand ALL more deeply, the metabolome in fasting plasma of 27 ALL patients before and after high-dose methotrexate therapies (consolidation therapy) including methotrexate and 6-mercaptopurine (6-MP) was investigated. Plasma metabolites were analyzed using liquid chromatography–tandem mass spectrometry (LC–MS). Orthogonal projections to latent structures discriminant analysis and significance analysis of microarrays were used to evaluate the metabolic changes. Pathway enrichment and co-expression network analyses were performed to identify clusters of molecules, and 2826 metabolites were identified. Among them, 38 metabolites were identified by univariate analysis, and 7 metabolites that were altered by conditioning therapy were identified by multivariate analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for pathway enrichment analysis. Among the enriched KEGG pathways, the 3 significantly altered metabolic pathways were pyrimidine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. In addition, L-phenylalanine was significantly correlated with blood urea nitrogen (BUN), and palmitoylcarnitine was correlated with aspartate aminotransferase (AST). In summary, consolidation therapy significantly affected pyrimidine- and phenylalanine-associated metabolic pathways in pediatric ALL patients. These findings may provide an insight into the role of metabolic profiling in consolidation treatment and as a potential for pediatric ALL patients.https://doi.org/10.1186/s40170-023-00302-6MetabolomicsAcute lymphoblastic leukemiaConsolidation therapy |
| spellingShingle | Jinqiu Fu Aijun Zhang Qinqin Liu Dong Li Xiaoming Wang Libo Si Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia Cancer & Metabolism Metabolomics Acute lymphoblastic leukemia Consolidation therapy |
| title | Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia |
| title_full | Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia |
| title_fullStr | Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia |
| title_full_unstemmed | Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia |
| title_short | Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia |
| title_sort | metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia |
| topic | Metabolomics Acute lymphoblastic leukemia Consolidation therapy |
| url | https://doi.org/10.1186/s40170-023-00302-6 |
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