Description:
<jats:title>Summary</jats:title><jats:p>Here, we report a high incidence of <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5</jats:italic> abnormalities observed in 32/68 (47%) of patients with genetically unclassified childhood precursor B‐cell acute lymphoblastic leukaemia (pre‐B <jats:styled-content style="fixed-case">ALL</jats:styled-content>). Various deletions, gains, mutations and rearrangements of <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5</jats:italic> 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 <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5</jats:italic>. Novel <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5‐<jats:styled-content style="fixed-case">RHOXF</jats:styled-content>2</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">PAX</jats:styled-content>5‐<jats:styled-content style="fixed-case">ELK</jats:styled-content>3</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5‐<jats:styled-content style="fixed-case">CBFA</jats:styled-content>2T2</jats:italic> rearrangements, which lead to aberrant expression of <jats:styled-content style="fixed-case">PAX</jats:styled-content>5, were also identified. <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5</jats:italic> rearrangements demonstrated a complex mechanism of formation including concurrent duplications/deletions of <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5</jats:italic> and its partner genes. Finally, the splice variant c.1013‐2A>G, seen in two patients with loss of one <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5</jats:italic> allele, was confirmed to be germ‐line in one patient and somatic in the other. <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5</jats:italic> alterations were also found to be clinically associated with a higher white blood cell count (<jats:italic>P</jats:italic> = 0·015). These findings contribute to the knowledge of <jats:italic><jats:styled-content style="fixed-case">PAX</jats:styled-content>5</jats:italic> alterations and their role in the pathogenesis of pre‐B <jats:styled-content style="fixed-case">ALL</jats:styled-content>.</jats:p>