Promising genes and variants to reduce chemotherapy adverse effects in acute lymphoblastic leukemia

Bárcenas-López, Diego Alberto; Mendiola-Soto, Diana Karen; Núñez-Enríquez, Juan Carlos; Mejı́a-Aranguré, Juan Manuel; Hidalgo‐Miranda, Alfredo; Jiménez-Morales, Silvia

doi:10.1016/j.tranon.2020.100978

Cited by 8 publications

(11 citation statements)

References 161 publications

(201 reference statements)

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“…Currently, chemotherapy, radiation therapy, and hematopoietic stem cell transplantation are being applied as general clinical therapies for the treatment of leukemia patients. However, the poor prognosis, drug resistance and serious side effects are hurdles to effective treatment and lead to frequent recurrences (Shimada 2019 ; Bárcenas-López et al 2021 ). Therefore, there is an urgent need to develop a new therapeutic agent with low side effects and high efficiency for the treatment of leukemia.…”

Section: Introductionmentioning

confidence: 99%

The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis

Park

Jeong

Han

et al. 2021

Animal Cells and Systems

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Although previous studies have shown anti-cancer activity of betulinic acid (BA), a pentacyclic triterpenoid, against various cancer lines, the underlying molecular mechanisms are not well elucidated. In this study, we evaluated the mechanisms involved in the anti-cancer efficacy of BA in U937 human myeloid leukemia cells. BA exerted a significant cytotoxic effect on U937 cells through blocking cell cycle arrest at the G2/M phase and inducing apoptosis, and that the intracellular reactive oxygen species (ROS) levels increased after treatment with BA. The down-regulation of cyclin A and cyclin B1, and up-regulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1 revealed the G2/M phase arrest mechanism of BA. In addition, BA induced the cytosolic release of cytochrome c by reducing the mitochondrial membrane potential with an increasing Bax/Bcl-2 expression ratio. BA also increased the activity of caspase-9 and -3, and subsequent degradation of the poly (ADP-ribose) polymerase. However, quenching of ROS by N -acetyl-cysteine, an ROS scavenger, markedly abolished BA-induced G2/M arrest and apoptosis, indicating that the generation of ROS plays a key role in inhibiting the proliferation of U937 cells by BA treatment. Taken together, our results provide a mechanistic rationale that BA exhibits anti-cancer properties in U937 leukemia cells through ROS-dependent induction of cell cycle arrest at G2/M phase and apoptosis.

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Section: Introductionmentioning

confidence: 99%

The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis

Park

Jeong

Han

et al. 2021

Animal Cells and Systems

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“…Some forms of leukemia are treatable, and have high survival rates, while others can be more aggressive and have lower survival rates. Prevention efforts often focus on avoiding known risk factors like exposure to carcinogens (e.g., benzene), maintaining a healthy lifestyle, and genetic counseling for individuals with a family history of leukemia or genetic predispositions (Bárcenas-López et al 2021).…”

Section: Risk Factors For Developing Leukemiamentioning

confidence: 99%

Pharmacogenomics of Leukemia; Unlocking Personalized Treatment Strategies

Nimra,

Robab,

Fawad Rasool

2023

Precis. Med. Com.

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Leukemia, a diverse group of blood cancers, continues to present significant challenges in diagnosis and treatment. Recent advancements in pharmacogenomics have opened new avenues for tailoring therapeutic strategies to individual patients' unique genetic and molecular characteristics. In leukemia, genetic polymorphisms have been identified that influence drug metabolism, efficacy, and the risk of adverse effects. Notable examples include TPMT variants affecting thiopurine treatment in acute lymphoblastic leukemia (ALL), UGT1A1 polymorphisms impacting irinotecan toxicity in acute myeloid leukemia (AML), and SLCO1B1 variants influencing methotrexate response in ALL. Targeted therapies have revolutionized leukemia treatment, focusing on specific genetic abnormalities. Tyrosine kinase inhibitors (TKIs) like imatinib have successfully treated chronic myeloid leukemia (CML) with the BCR-ABL fusion gene. Similarly, immunotherapies, such as CAR T-cell therapy, reshape treatment paradigms for B-cell ALL. The personalized approach minimizes adverse effects while optimizing treatment efficacy. Moreover, genetic markers are aiding in identifying patients at higher risk of developing cardiotoxicity from anthracycline chemotherapy. This article provides an overview of the evolving landscape of pharmacogenomics in leukemia, highlighting key findings and trends. Combinatorial therapies, biomarker discovery, and patient-centric care are expected to enhance outcomes and survivorship.

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“…Reducing these risks may improve outcomes [ 3 ]. Studies have addressed the mitigation of adverse events resulting from complex ALL therapies [ 4 , 5 ] in an attempt to reduce mortality from adverse events.…”

Section: Introductionmentioning

confidence: 99%

Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia

Zhang

Liu

et al. 2023

Cancer Metab

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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.

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Promising genes and variants to reduce chemotherapy adverse effects in acute lymphoblastic leukemia

Cited by 8 publications

References 161 publications

The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis

The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis

Pharmacogenomics of Leukemia; Unlocking Personalized Treatment Strategies

Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia

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