PAX5, a member of the Paired Box (PAX) transcription factor family, is an essential factor for B-lineage identity during lymphoid differentiation [3]. It controls gene expression profiles crucial for cellular viability, proliferation, and differentiation, and is involved in B-cell development pathways [3]. Given its role in B-cell development, its aberrant expression is associated with hematological and other cancers [3]. Genetic models, such as KO/CKO mouse models, can be valuable for studying PAX5.

In B-progenitor acute lymphoblastic leukemia (B-ALL), two subtypes have frequent PAX5 alterations. The PAX5alt subtype (7.4%) has diverse PAX5 changes like rearrangements, intragenic amplifications or mutations, and another subtype is defined by PAX5 p.Pro80Arg and biallelic PAX5 alterations. The p.Pro80Arg impairs B lymphoid development and promotes B-ALL development with biallelic Pax5 alteration in vivo [1]. Also, PAX5 is frequently mutated in ALL, involved in chromosomal rearrangements and translocations, and its mutations interact with genes like ETV6 and FOXP1 influencing B-cell development. For example, PAX5/ETV6 has been observed in B-ALL patients and mouse models, and the interaction between PAX5 and FOXP1 negatively suppresses the Pax5 gene in B-ALL patients. Additionally, ELN-PAX5 and PML-PAX5 fusions lead to adverse effects on B-cell differentiation [2].

In conclusion, PAX5 is a master regulator of B-cell development, controlling gene transcription during B-lymphopoiesis. Its role in B-cell commitment and differentiation is crucial, and its dysregulation is linked to B-ALL. Mouse models, especially those with Pax5 knockout or conditional knockout, have been instrumental in revealing its role in leukemogenesis, providing insights into the mechanisms underlying B-ALL development [1,2,4].

References:

1. Gu, Zhaohui, Churchman, Michelle L, Roberts, Kathryn G, Hunger, Stephen P, Mullighan, Charles G. 2019. PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia. In Nature genetics, 51, 296-307. doi:10.1038/s41588-018-0315-5. https://pubmed.ncbi.nlm.nih.gov/30643249/

2. Fouad, Fatma Mohamed, Eid, Jehane I. . PAX5 fusion genes in acute lymphoblastic leukemia: A literature review. In Medicine, 102, e33836. doi:10.1097/MD.0000000000033836. https://pubmed.ncbi.nlm.nih.gov/37335685/

3. Nasri Nasrabadi, Parinaz, Martin, Danick, Gharib, Ehsan, Robichaud, Gilles A. 2022. The Pleiotropy of PAX5 Gene Products and Function. In International journal of molecular sciences, 23, . doi:10.3390/ijms231710095. https://pubmed.ncbi.nlm.nih.gov/36077495/

4. Medvedovic, Jasna, Ebert, Anja, Tagoh, Hiromi, Busslinger, Meinrad. . Pax5: a master regulator of B cell development and leukemogenesis. In Advances in immunology, 111, 179-206. doi:10.1016/B978-0-12-385991-4.00005-2. https://pubmed.ncbi.nlm.nih.gov/21970955/