PAX5 alterations in genetically unclassified childhood Precursor B‐cell acute lymphoblastic leukaemia. (26th June 2015)

• Record Type: Journal Article
• Authors: Stasevich, Irina; Inglott, Sarah; Austin, Nicola; Chatters, Steve; Chalker, Jane; Addy, Dilys; Dryden, Carryl; Ancliff, Philip; Ford, Anthony; Williams, Owen; Kempski, Helena
• Is Part Of: British journal of haematology. Volume 171:Number 2(2015:Oct.)
• Page Start: 263
• Page End: 272
• Publication Date: 2015-06-26
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13543
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh13543-abs-0001"> <title>Summary</title> <p>Here, we report a high incidence of <italic>PAX5</italic> 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 <italic>PAX5</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 <italic>PAX5</italic>. Novel <italic>PAX5‐RHOXF2</italic>, <italic> PAX5‐ELK3</italic> and <italic>PAX5‐CBFA2T2</italic> rearrangements, which lead to aberrant expression of PAX5, were also identified. <italic>PAX5</italic> rearrangements demonstrated a complex mechanism of formation including concurrent duplications/deletions of <italic>PAX5</italic> and its partner genes. Finally, the splice variant c.1013‐2A&gt;G, seen in two patients with loss of one <italic>PAX5</italic> allele, was confirmed to be germ‐line in one patient and somatic in the other. <italic>PAX5</italic> alterations were also found to be clinically associated with a higher white blood cell count (<italic>P</italic> = 0·015). These findings contribute to the knowledge of <italic>PAX5</italic> alterations and their role in the pathogenesis of pre‐B ALL.</p> </abstract>