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Among its defining hallmarks, metabolic reprogramming has emerged as a critical determinant of disease initiation, progression, therapeutic resistance, and relapse. Leukemic cells reshape their metabolic pathways to meet the survival demands of rapid proliferation. This review provides a comprehensive synthesis of recent advances on the characteristic mechanisms of metabolic reprogramming and targeted intervention strategies for different subtypes of pediatric AL (ALL\/AML). Each subtype exhibits distinct metabolic pathways and key molecular abnormalities that influence disease progression and treatment outcomes. Importantly, the strategic targeting of key metabolic nodes has demonstrated considerable potential in eradicating leukemic cells. A deeper understanding of metabolic reprogramming mechanisms in leukemic cells is therefore essential, as it offers valuable insights into overcoming drug resistance, reducing relapse rates, and informing the development of innovative therapeutic strategies.<\/jats:p>","DOI":"10.1002\/1545-5017.70227","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T05:33:06Z","timestamp":1773639186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Research Progress of Metabolic Reprogramming in Childhood Acute Leukemia"],"prefix":"10.1002","volume":"73","author":[{"given":"Yuzhi","family":"Yan","sequence":"first","affiliation":[{"name":"Pediatric Department of Urology and Immunology Children's Medical Center The Affiliated Hospital of Southwest Medical University  Luzhou Sichuan China"},{"name":"Sichuan Clinical Research Center for Birth Defects  Luzhou Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Pediatric Department of Urology and Immunology Children's Medical Center The Affiliated Hospital of Southwest Medical University  Luzhou Sichuan China"},{"name":"Sichuan Clinical Research Center for Birth Defects  Luzhou Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.8.6.519"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.124.3215.269"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.123.3191.309"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00339-6"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01541-0"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.009"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3772"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09595"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.03.008"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.12.013"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.01.013"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3038"},{"issue":"11","key":"e_1_2_10_15_1","first-page":"845","article-title":"Metabolism of Neoplastic Tissue. 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