{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:15:25Z","timestamp":1791918925777,"version":"4.3.4"},"reference-count":170,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T00:00:00Z","timestamp":1610150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/01971"],"award-info":[{"award-number":["PI14\/01971"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","award":["GC16173697BIGA"],"award-info":[{"award-number":["GC16173697BIGA"]}]},{"name":"CERCA Program\/Generalitat de Catalunya","award":["2017 SGR288"],"award-info":[{"award-number":["2017 SGR288"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Acute lymphoblastic leukemia (ALL) is a malignant clonal expansion of lymphoid hematopoietic precursors that exhibit developmental arrest at varying stages of differentiation. Similar to what occurs in solid cancers, transformation of normal hematopoietic precursors is governed by a multistep oncogenic process that drives initiation, clonal expansion and metastasis. In this process, alterations in genes encoding proteins that govern processes such as cell proliferation, differentiation, and growth provide us with some of the clearest mechanistic insights into how and why cancer arises. In such a scenario, deletions in the 9p21.3 cluster involving CDKN2A\/ARF\/CDKN2B genes arise as one of the oncogenic hallmarks of ALL. Deletions in this region are the most frequent structural alteration in T-cell acute lymphoblastic leukemia (T-ALL) and account for roughly 30% of copy number alterations found in B-cell-precursor acute lymphoblastic leukemia (BCP-ALL). Here, we review the literature concerning the involvement of the CDKN2A\/B genes as a prognosis marker of good or bad response in the two ALL subtypes (BCP-ALL and T-ALL). We compare frequencies observed in studies performed on several ALL cohorts (adult and child), which mainly consider genetic data produced by genomic techniques. We also summarize what we have learned from mouse models designed to evaluate the functional involvement of the gene cluster in ALL development and in relapse\/resistance to treatment. Finally, we examine the range of possibilities for targeting the abnormal function of the protein-coding genes of this cluster and their potential to act as anti-leukemic agents in patients.<\/jats:p>","DOI":"10.3390\/genes12010079","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T19:55:56Z","timestamp":1610308556000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Yin and Yang-Like Clinical Implications of the CDKN2A\/ARF\/CDKN2B Gene Cluster in Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"12","author":[{"given":"Celia","family":"Gonz\u00e1lez-Gil","sequence":"first","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona (UAB), 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Ribera","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona (UAB), 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-6024","authenticated-orcid":false,"given":"Josep Maria","family":"Ribera","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona (UAB), 08916 Badalona, Spain"},{"name":"Clinical Hematology Department, ICO-Hospital Germans Trias i Pujol, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eul\u00e0lia","family":"Genesc\u00e0","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona (UAB), 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1056\/NEJMoa0900386","article-title":"Treating Childhood Acute Lymphoblastic Leukemia without Cranial Irradiation","volume":"360","author":"Pui","year":"2009","journal-title":"N. 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