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 (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.

Augmenter of liver regeneration promotes drug resistance of acute lymphoblastic leukemia through the alteration of mitochondrial functions and the inhibition of the mitochondrial apoptosis pathway

“…Drug resistance is associated with various factors, and mitochondrial dysfunction is one of them. Targeting mitochondria has been a strategy for anti‐cancer therapy 31 and many studies confirmed its potential use as a treatment option for leukemia patients 9,10,32 . Therefore, targeting ALR may alter the mitochondrial function in T‐ALL which may prevent drug resistance in T‐ALL cells.…”

“…Drug resistance is a crucial element of the relapse 7,8 and how to sensitize cancer cells to drugs' treatments is a question to ponder. Mitochondria are one such important target in ALL treatment, 9 and targeting mitochondrial respiration improves T‐ALL cells' sensitivity to chemotherapy 10 …”

“…Mitochondria are one such important target in ALL treatment, 9 and targeting mitochondrial respiration improves T-ALL cells' sensitivity to chemotherapy. 10 Our previous works brought to our attention a protein, related to mitochondrial function, known as Augmenter of liver regeneration (ALR). ALR is a cytokine found in mouse liver that can stimulate liver regeneration.…”

Metabolomics analysis reveals characteristic metabolites in different levels of oxaliplatin‐induced neurotoxicity

“…To prepare the quality control (QC) samples, we pooled ten microliters of each sample. The extraction procedure for the QC samples was performed in the same manner as described earlier [32].…”