{"doi":"10.3389/fonc.2022.1023606","title":"PAX5 alterations in B-cell acute lymphoblastic leukemia","abstract":"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). PAX5 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 PAX5 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 PAX5 genetic lesions, such as the one defined by a distinct gene expression profile and PAX5 P80R mutation, which is an exemplar leukemia entity driven by a missense mutation. Although altered PAX5 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 PAX5 variants alone or concomitant with other genetic lesions in driving B-cell malignancy, indicating the altered PAX5 and deregulated genes may serve as potential therapeutic targets in certain B-ALL cases.","journal":"Frontiers in Oncology","year":2022,"id":240566,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":253485,"name":"Zhaohui Gu","orcid":"0000-0003-1581-1327","position":1,"is_corresponding":false},{"id":869234,"name":"Zhilian Jia","orcid":null,"position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T00:22:51.435773Z","pmid":"36387144","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}