{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:06:00Z","timestamp":1790899560766,"version":"4.1.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>PAX5, a master regulator of B cell development and maintenance, is one of the most common targets of genetic alterations in B-cell acute lymphoblastic leukemia (B-ALL). <jats:italic>PAX5<\/jats:italic> alterations consist of copy number variations (whole gene, partial, or intragenic), translocations, and point mutations, with distinct distribution across B-ALL subtypes. The multifaceted functional impacts such as haploinsufficiency and gain-of-function of PAX5 depending on specific variants have been described, thereby the connection between the blockage of B cell development and the malignant transformation of normal B cells has been established. In this review, we provide the recent advances in understanding the function of PAX5 in orchestrating the development of both normal and malignant B cells over the past decade, with a focus on the <jats:italic>PAX5<\/jats:italic> alterations shown as the initiating or driver events in B-ALL. Recent large-scale genomic analyses of B-ALL have identified multiple novel subtypes driven by <jats:italic>PAX5<\/jats:italic> genetic lesions, such as the one defined by a distinct gene expression profile and <jats:italic>PAX5<\/jats:italic> P80R mutation, which is an exemplar leukemia entity driven by a missense mutation. Although altered <jats:italic>PAX5<\/jats:italic> is shared as a driver in B-ALL, disparate disease phenotypes and clinical outcomes among the patients indicate further heterogeneity of the underlying mechanisms and disturbed gene regulation networks along the disease development. In-depth mechanistic studies in human B-ALL and animal models have demonstrated high penetrance of <jats:italic>PAX5<\/jats:italic> variants alone or concomitant with other genetic lesions in driving B-cell malignancy, indicating the altered <jats:italic>PAX5<\/jats:italic> and deregulated genes may serve as potential therapeutic targets in certain B-ALL cases.<\/jats:p>","DOI":"10.3389\/fonc.2022.1023606","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T05:47:22Z","timestamp":1666676842000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":47,"title":["PAX5 alterations in B-cell acute lymphoblastic leukemia"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhilian","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05690","article-title":"Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia","volume":"446","author":"Mullighan","year":"2007","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404691","article-title":"High-resolution genomic profiling of childhood ALL reveals novel recurrent genetic lesions affecting pathways involved in lymphocyte differentiation and cell cycle 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