{"doi":"10.1002/cac2.12080","title":"Targeting lactate dehydrogenase A (\n                    <i>LDHA</i>\n                    ) exerts antileukemic effects on T‐cell acute lymphoblastic leukemia","abstract":"<h4>Background</h4>T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon and aggressive subtype of acute lymphoblastic leukemia (ALL). In the serum of T-ALL patients, the activity of lactate dehydrogenase A (LDHA) is increased. We proposed that targeting LDHA may be a potential strategy to improve T-ALL outcomes. The current study was conducted to investigate the antileukemic effect of LDHA gene-targeting treatment on T-ALL and the underlying molecular mechanism.<h4>Methods</h4>Primary T-ALL cell lines Jurkat and DU528 were treated with the LDH inhibitor oxamate. MTT, colony formation, apoptosis, and cell cycle assays were performed to investigate the effects of oxamate on T-ALL cells. Quantitative real-time PCR (qPCR) and Western blotting analyses were applied to determine the related signaling pathways. A mitochondrial reactive oxygen species (ROS) assay was performed to evaluate ROS production after T-ALL cells were treated with oxamate. A T-ALL transgenic zebrafish model with LDHA gene knockdown was established using CRISPR/Cas9 gene-editing technology, and then TUNEL, Western blotting, and T-ALL tumor progression analyses were conducted to investigate the effects of LDHA gene knockdown on T-ALL transgenic zebrafish.<h4>Results</h4>Oxamate significantly inhibited proliferation and induced apoptosis of Jurkat and DU528 cells. It also arrested Jurkat and DU528 cells in G0/G1 phase and stimulated ROS production (all P < 0.001). Blocking LDHA significantly decreased the gene and protein expression of c-Myc, as well as the levels of phosphorylated serine/threonine kinase (AKT) and glycogen synthase kinase 3 beta (GSK-3β) in the phosphatidylinositol 3'-kinase (PI3K) signaling pathway. LDHA gene knockdown delayed disease progression and down-regulated c-Myc mRNA and protein expression in T-ALL transgenic zebrafish.<h4>Conclusion</h4>Targeting LDHA exerted an antileukemic effect on T-ALL, representing a potential strategy for T-ALL treatment.","journal":"Cancer Communications","year":2020,"id":9170,"datarank":0.5742962094733643,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.0,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.036,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-08-21","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":7409,"name":"Yafei Yin","orcid":"0000-0002-0171-844X","position":1,"is_corresponding":false},{"id":78455,"name":"Yifang Yi","orcid":null,"position":2,"is_corresponding":false},{"id":1666,"name":"Zhao Cheng","orcid":"0000-0002-5801-1517","position":3,"is_corresponding":false},{"id":78456,"name":"Wenyong Kuang","orcid":null,"position":4,"is_corresponding":false},{"id":1664,"name":"Ruijuan Li","orcid":"0000-0002-2278-4622","position":5,"is_corresponding":false},{"id":78457,"name":"Haiying Zhong","orcid":"0000-0002-2257-887X","position":6,"is_corresponding":false},{"id":78458,"name":"Yajuan Cui","orcid":"0000-0001-7086-2819","position":7,"is_corresponding":false},{"id":78459,"name":"Lingli Yuan","orcid":"0000-0002-9293-6388","position":8,"is_corresponding":false},{"id":78460,"name":"Fanjie Gong","orcid":null,"position":9,"is_corresponding":false},{"id":1663,"name":"Zhihua Wang","orcid":null,"position":10,"is_corresponding":false},{"id":30887,"name":"Alexandra P. Lewis","orcid":"0000-0002-6195-4786","position":11,"is_corresponding":false},{"id":1667,"name":"Hongling Peng","orcid":"0000-0003-2770-5150","position":12,"is_corresponding":false},{"id":78461,"name":"Guangsen Zhang","orcid":"0000-0002-3812-9892","position":13,"is_corresponding":false},{"id":1669,"name":"Wang Zh","orcid":"0000-0002-1800-2384","position":14,"is_corresponding":false},{"id":78454,"name":"Haizhi Yu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}