PAX5, a member of the Paired Box (PAX) transcription factor family, is essential for B-lineage identity during lymphoid differentiation. It controls gene expression profiles related to cellular viability, proliferation, and differentiation, and is crucial in B-cell development [3]. Aberrant PAX5 expression is associated with hematological and other cancers [3].

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 interacts with genes like ETV6 and FOXP1 influencing B-cell development [2]. In B-ALL, PAX5 fusion genes prevent PAX5 gene transcription, making it an important target for leukemia progression study and B-ALL diagnosis [2]. Additionally, in B-ALL, PAX5 epigenetically controls CD58 transcription and affects blinatumomab response, with the PAX5 P80R mutation reducing CD58 expression and blinatumomab sensitivity [4].

In conclusion, PAX5 is a master regulator of B-cell development, controlling gene transcription to guide B-cell commitment and development. Its dysregulation is implicated in B-ALL, and studies on PAX5-related alterations in B-ALL mouse models help understand the leukemogenesis mechanism, providing potential insights for diagnosis and treatment of this hematological malignancy [1,2,4].