{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T10:44:21Z","timestamp":1784371461029,"version":"3.55.0"},"reference-count":45,"publisher":"Portland Press Ltd.","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"by Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","award":["CF-2023-I-811 CF-2023-I-2755"],"award-info":[{"award-number":["CF-2023-I-811 CF-2023-I-2755"]}]},{"name":"E022 Program, National Institute of Pediatrics, Mexico City, Mexico","award":["2019\/072 2022\/067 2025\/025"],"award-info":[{"award-number":["2019\/072 2022\/067 2025\/025"]}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute lymphoblastic leukemia, particularly the T-cell subtype, remains associated with poor outcomes in relapsed and adult patients, highlighting the need for novel therapeutic strategies. Metabolic reprogramming, especially glycolytic dependence, represents a promising target. Triosephosphate isomerase (TPI), a key glycolytic enzyme, undergoes cancer-associated post-translational modifications (PTMs), including deamidation and phosphorylation. Here, we evaluated the potential of proton pump inhibitors (PPIs), particularly rabeprazole (Rbz), to selectively target PTM-bearing TPI isoforms in Jurkat cell model. Recombinant TPI variants engineered to mimic PTMs exhibited increased reactivity toward thiol-modifying agents and higher predicted binding affinities for PPI compared with wild-type TPI. Consistent with these properties, biochemical assays demonstrated preferential inhibition of the deamidation- and phosphorylation-mimicking proteins, with Rbz significantly reducing their enzymatic activity. Native gel electrophoresis of Jurkat cells protein extracts revealed drug-induced accumulation of acidic TPI isoforms, whereas normal T lymphocytes predominantly retained unmodified TPI. Rbz selectively impaired intracellular TPI activity and viability in Jurkat cells, effects enhanced by dichloroacetate (DCA) co-treatment. This inhibition correlated with marked accumulation of methylglyoxal and advanced glycation end products. Finally, combined DCA\u2013Rbz treatment induced extensive apoptotic death in Jurkat cells while sparing normal lymphocytes. These findings identify PTM-bearing TPI isoforms as selective metabolic vulnerabilities in Jurkat cells and support the potential repurposing of thiol-modifying agents, particularly, Rbz, as targeted antileukemic strategies.<\/jats:p>","DOI":"10.1042\/bcj20253451","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:37:36Z","timestamp":1770043056000},"page":"319-344","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Post-translational modifications of triosephosphate isomerase reveal metabolic vulnerabilities in T-ALL: effect of combining dichloroacetic acid and the PPI rabeprazole"],"prefix":"10.1042","volume":"483","author":[{"given":"Yoalli","family":"Mart\u00ednez-P\u00e9rez","sequence":"first","affiliation":[{"name":"1Tecnol\u00f3gico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico City 14380, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"De la Mora-De la Mora","sequence":"additional","affiliation":[{"name":"2Laboratorio de Biomol\u00e9culas y Salud Infantil, Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Hern\u00e1ndez-Alc\u00e1ntara","sequence":"additional","affiliation":[{"name":"3Departamento de Bioqu\u00edmica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Apartado Postal 70-159, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"L\u00f3pez-Herrera","sequence":"additional","affiliation":[{"name":"4Laboratorio de Inmunodeficiencias, Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzhel","family":"Garc\u00eda-Torres","sequence":"additional","affiliation":[{"name":"2Laboratorio de Biomol\u00e9culas y Salud Infantil, Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00fal","family":"G\u00f3mez-Manzo","sequence":"additional","affiliation":[{"name":"5Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Olaya-Vargas","sequence":"additional","affiliation":[{"name":"6Trasplante de C\u00e9lulas Madre y Terapia Celular, Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Le\u00f3n-Avila","sequence":"additional","affiliation":[{"name":"7Departamento de Zoolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Carpio y Plan de Ayala S\/N, Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9\u00a0Manuel","family":"Hern\u00e1ndez-Hernandez","sequence":"additional","affiliation":[{"name":"8Departamento de Biolog\u00eda Celular. CINVESTAV, Av. IPN 2508. Col., San Pedro Zacatenco, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Gonz\u00e1lez-Rubio","sequence":"additional","affiliation":[{"name":"9Licenciatura en Biolog\u00eda, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.\u00a0Yusiel","family":"Flores-Braulio","sequence":"additional","affiliation":[{"name":"9Licenciatura en Biolog\u00eda, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis\u00a0A.","family":"Flores-L\u00f3pez","sequence":"additional","affiliation":[{"name":"2Laboratorio de Biomol\u00e9culas y Salud Infantil, Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"},{"name":"10Laboratorio de Biomol\u00e9culas y Salud Infantil, SECIHTI-Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2058-5707","authenticated-orcid":false,"given":"Sergio","family":"Enr\u00edquez-Flores","sequence":"additional","affiliation":[{"name":"2Laboratorio de Biomol\u00e9culas y Salud Infantil, Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"2026021810313710700_B1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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