PAX 5 alterations in genetically unclassified childhood Precursor B‐cell acute lymphoblastic leukaemia

Summary Here, we report a high incidence of PAX 5 abnormalities observed in 32/68 (47%) of patients with genetically unclassified childhood precursor B‐cell acute lymphoblastic leukaemia (pre‐B ALL ). Various deletions, gains, mutations and rearrangements of PAX 5 comprised 45%, 12%, 29% and 14%, respectively, of the abnormalities found. 28% of patients showed more than one abnormality of the gene, implying bi‐allelic impairment of PAX 5 . Novel PAX 5‐ RHOXF 2 , PAX 5‐ ELK 3 and PAX 5‐ CBFA 2T2 rearrangements, which lead to aberrant expression of PAX 5, were also identified. PAX 5 rearrangements demonstrated a complex mechanism of formation including concurrent duplications/deletions of PAX 5 and its partner genes. Finally, the splice variant c.1013‐2A>G, seen in two patients with loss of one PAX 5 allele, was confirmed to be germ‐line in one patient and somatic in the other. PAX 5 alterations were also found to be clinically associated with a higher white blood cell count ( P  = 0·015). These findings contribute to the knowledge of PAX 5 alterations and their role in the pathogenesis of pre‐B ALL .