{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T09:01:07Z","timestamp":1785315667480,"version":"3.55.0"},"reference-count":92,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SECIHTI","award":["470774"],"award-info":[{"award-number":["470774"]}]},{"name":"SECIHTI","award":["4002172"],"award-info":[{"award-number":["4002172"]}]},{"name":"FORDECYT-PRONACES 2023","award":["CF-2023-G-749"],"award-info":[{"award-number":["CF-2023-G-749"]}]},{"name":"LANCAD","award":["32-2025"],"award-info":[{"award-number":["32-2025"]}]},{"name":"Bioinformatic Unit from the Molecular Biomedicine Laboratory-FCQB-UAGro"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most frequent malignancy of childhood; worldwide, 487,294 new cases and 305,405 deaths were reported in 2022, including more than 5000 new cases in Mexico. Chemotherapy, delivered in induction, consolidation and maintenance phases, remains the mainstay of treatment, yet 10\u201320% of patients relapse after induction because of chemoresistance, whose molecular basis is still incompletely understood. Methods: This retrospective study aimed to identify proteins associated with resistance to vincristine (VCR) and methotrexate (MTX) administered during the induction phase, using LC\u2013MS\/MS proteomics and bioinformatic analysis of treatment-naive bone marrow aspirates from responders and nonresponders. Results: Nonresponders showed a distinct proteomic profile, with deregulated processes converging on cytoskeletal structure and dynamics, nucleic acid metabolism, DNA repair and RNA processing. Within these processes, thymidine phosphorylase (TYMP) and gelsolin (GSN) emerged as differentially expressed proteins, both consistently overexpressed in nonresponders at the individual-patient level. Conclusions: We conclude that cytoskeletal remodeling and nucleotide metabolism are prominent features of intrinsic chemoresistance in pediatric B-ALL, and that TYMP and GSN represent candidate biomarkers of nonresponse to VCR- and MTX-based induction that warrant validation by orthogonal methods in independent, adequately powered cohorts.<\/jats:p>","DOI":"10.3390\/ph19081167","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:26:23Z","timestamp":1785115583000},"page":"1167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic Profiling of Bone Marrow Aspirates from Patients with Methotrexate- and Vincristine-Resistant B-Cell Acute Lymphoblastic Leukemia: A Retrospective Analysis"],"prefix":"10.3390","volume":"19","author":[{"given":"Esli Janai","family":"Flores-Palma","sequence":"first","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0361-437X","authenticated-orcid":false,"given":"Diana Laura","family":"Gonzalez-Tolentino","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7889-1681","authenticated-orcid":false,"given":"Sergio","family":"Encarnaci\u00f3n-Guevara","sequence":"additional","affiliation":[{"name":"Centro de Ciencias Gen\u00f3micas, UNAM, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3601-3893","authenticated-orcid":false,"given":"Jeovanis","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Lund University, 22242 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1449-1145","authenticated-orcid":false,"given":"Ramiro","family":"Alonso-Bastida","sequence":"additional","affiliation":[{"name":"Centro de Ciencias Gen\u00f3micas, UNAM, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel Gabriel","family":"Mart\u00ednez-Batallar","sequence":"additional","affiliation":[{"name":"Centro de Ciencias Gen\u00f3micas, UNAM, Cuernavaca 62210, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica Virginia","family":"Saavedra-Herrera","sequence":"additional","affiliation":[{"name":"Instituto Estatal de Cancerolog\u00eda \u201cDr. Arturo Beltr\u00e1n Ortega\u201d, Acapulco 39570, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6578-8607","authenticated-orcid":false,"given":"Elo\u00edsa","family":"Ibarra-Sierra","sequence":"additional","affiliation":[{"name":"Instituto Estatal de Cancerolog\u00eda \u201cDr. Arturo Beltr\u00e1n Ortega\u201d, Acapulco 39570, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8367-9730","authenticated-orcid":false,"given":"Yazm\u00edn","family":"G\u00f3mez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3937-335X","authenticated-orcid":false,"given":"Berenice","family":"Illades-Aguiar","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0986-9453","authenticated-orcid":false,"given":"Olga Lilia","family":"Garibay-Cerdenares","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"},{"name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI), SECIHTI-Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3345-5859","authenticated-orcid":false,"given":"Marco Antonio","family":"Leyva-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina Molecular, Facultad de Ciencias Qu\u00edmico Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo 39090, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brown, G. 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