Recurrent PAX5::ZCCHC7 rearrangement in B-cell acute lymphoblastic leukemia

The PAX5 (paired box 5) gene encodes a transcription factor that plays a critical role in B-cell development. PAX5 rearrangement is a recurrent abnormality seen in about 1.0-2.5% of B-cell acute lymphoblastic leukemia (B-ALL) cases. In this study, we presented 3 cases of B-ALL harboring PAX5::ZCCHC7 rearrangement. We subsequently reviewed the literature and identified 45 additional B-ALL cases with PAX5::ZCCHC7. Our data showed that the majority of B-ALL patients with PAX5::ZCCHC7 were observed in various subtypes of B-ALL, including BCR::ABL1-like, BCR::ABL1, ETV6::RUNX1 and others. In B-ALL, PAX5::ZCCHC7 was always co-occur with other subtype-defining rearrangements, which as the sole abnormality in only 8 patients, with the remaining 34 patients harboring CRLF2, JAK2, TCF3 or other rearrangements. In PAX5::ZCCHC7, the PAX5 breakpoints are mainly between exon 1 and 2 (30/51). As a result, nearly all PAX5 protein domains are lost in PAX5::ZCCHC7, suggesting that the PAX5::ZCCHC7 seems to disrupt PAX5 similarly to a PAX5 deletion. In summary, the PAX5::ZCCHC7 is a recurrent genetic aberration in B-ALL and seems to act as an additional genetic abnormality of subtype-defining aberration. Whether the PAX5::ZCCHC7 could act as a leukemia-initiating event or not needs further investigation.