PAX5, located on 9p13, belongs to the PAX gene family and encodes for a transcription factor essential for B lymphoid cell commitment. It functions both as a transcriptional activator and repressor of different target genes involved in lineages development. PAX5 has been recently reported to be target of aberrancies (including point mutation, deletions, and gene fusions), in approximately 30% of pediatric patients affected by BCP-ALL, the most frequent leukemia subset in children. Translocations are estimated to occur at an incidence of 2-3%, with a variety of partner genes, encoding for transcription factors (TEL, PML, FOXP1), kinases (JAK2), structural proteins (ELN, POM121) or molecules of unknown function (C20orf112, AUTS2).

We performed a FISH-based study on an Italian cohort of BCP-ALL patients having 9p13 chromosomal rearrangement (as a hallmark of PAX5 rearrangement), and we identified novel PAX5 partner genes. Two pediatric patients were harboring a t(7;9)(q11.2;p13.2) with a PAX5/AUTS2 fusion transcript, thus confirming its recurrent alteration in pediatric B-ALL. Three novel partner genes of PAX5 were identified by FISH. SOX5 was found as a PAX5 partner in a pediatric patient harboring a dic(9;12)(p13;p13) chromosome. A further patient, showing a t(9;12)(p13;q34) translocation, revealed PAX5 as fused to a novel transcript isoform of CHFR, a gene widely expressed in a library of normal tissues. A third partner was identified in an adult B-ALL case, which showed a deletion within the short arm of chromosome 9, leading to the fusion of PAX5 to MLLT3.

A fourth PAX-rearranged case, involving POM121C (different from the already described POM121) as fused to PAX5 in a t(7;9)(q11;p13) translocation, was identified by a RNAseq approach on BCP-ALL cases without known prognostic features. The breakpoint on chromosome 7q11 is similar to the one associated with PAX5/AUTS2.

An accurate FISH analysis was performed on bone marrow cells of all cases to dissect the genomic breakpoints and the structure of the rearrangements. The fusion genes were cloned by 5’ and/or 3’ RACE PCR, confirmed by sequencing and verified by RT-PCR with specific primers on the source material. PAX5-translocated cases were further characterized by genome-wide Single Nucleotide Polymorphism array. Interestingly, Copy Number Variation analysis showed that a limited number of cooperative genetic lesions were present in addition to the translocation event, thus suggesting a primary role of the PAX rearrangement in leukemogenesis.

We therefore hypothesize that PAX5 alterations may represent single genetic aberration events in a simple background, rather than being part of a complex scenario of cooperating genetic lesions involved in leukemogenesis. A common pathway for all PAX5 genomic lesions still need to be elucidated.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.