{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:57:06Z","timestamp":1770188226154,"version":"3.49.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Acute lymphoblastic leukemia (ALL) is a heterogeneous malignancy characterized by various genomic alterations playing a crucial role in disease classification, prognosis, and response to treatment. However, molecular diagnosis and effective management of this hematological malignancy remain a major challenge, particularly in developing countries, including Tunisia. In this study, we aimed to conduct a detailed analysis of copy number alterations (CNAs) associated with ALL in a cohort of 60 primary samples from Tunisian patients. Using multiplex ligation-dependent probe amplification (MLPA), major genetic lesions, including\n                    <jats:italic>IKZF1<\/jats:italic>\n                    ,\n                    <jats:italic>CDKN2A\/2B<\/jats:italic>\n                    ,\n                    <jats:italic>PAX5<\/jats:italic>\n                    ,\n                    <jats:italic>ETV6<\/jats:italic>\n                    ,\n                    <jats:italic>BTG1,<\/jats:italic>\n                    and genes located in the\n                    <jats:italic>PAR1<\/jats:italic>\n                    region, were analyzed and their associations with clinical and laboratory features, as well as survival outcomes, were also evaluated. Our analysis revealed that 70% of patients had deletions and\/or amplifications in at least one gene. The most frequently observed deletions were in\n                    <jats:italic>CDKN2A\/2B<\/jats:italic>\n                    (33.3%, n\u2009=\u200920),\n                    <jats:italic>IKZF1<\/jats:italic>\n                    (30%, n\u2009=\u200918), and\n                    <jats:italic>PAX5<\/jats:italic>\n                    genes (25%, n\u2009=\u200915).\n                    <jats:italic>BTG1<\/jats:italic>\n                    deletions were significantly associated with female gender,\n                    <jats:italic>IKZF1<\/jats:italic>\n                    deletions were more frequent in adult patients, in those with elevated white blood cell (WBC) counts, and in cases involving the\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    translocation, while duplications of the\n                    <jats:italic>PAR1<\/jats:italic>\n                    region were significantly associated with hyperdiplo\u00efdy. Regarding treatment response, cases of\n                    <jats:italic>IKZF1<\/jats:italic>\n                    deletions showed a significant association with poor glucocorticoid response (GC) at day 8 of treatment and positive minimal residual disease (MRD) rates at days 33 and 63, particularly in B-ALL cases. Furthermore, patients with\n                    <jats:italic>IKZF1<\/jats:italic>\n                    deletions were associated with significantly lower survival rates in both univariate and multivariate analyses compared to those without these deletions. Additionally, the integration of\n                    <jats:italic>IKZF1<\/jats:italic>\n                    deletion status into risk stratification models revealed markedly different survival outcomes, highlighting its potential interest in developing new stratification algorithms. These results underscore the critical importance of molecular profiling, particularly\n                    <jats:italic>IKZF1<\/jats:italic>\n                    status, for improving outcomes in ALL patients in Tunisia.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0340696","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:22:33Z","timestamp":1770142953000},"page":"e0340696","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic characterization and prognostic significance of copy number alterations in Tunisian patients with acute lymphoblastic leukemia"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6907-0444","authenticated-orcid":true,"given":"Ameni","family":"Bedoui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wajdi","family":"Ayadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nour","family":"Louati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imen","family":"Frikha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosra","family":"Fakhfakh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahmi","family":"Smaoui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Gargouri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikram","family":"Ben Amor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moez","family":"Elloumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moez","family":"Mdhaffar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raja","family":"Mokdad Gargouri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"pone.0340696.ref001","volume-title":"Acute lymphocytic leukemia","author":"Y Puckett","year":"2025"},{"issue":"1","key":"pone.0340696.ref002","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1182\/asheducation-2018.1.137","article-title":"Genetics and prognosis of ALL in children vs adults","volume":"2018","author":"KG Roberts","year":"2018","journal-title":"Hematology Am Soc Hematol Educ 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