Deletion of PAX5 Is Frequently Accompanied by CDKN2A Deletion but Not by ETV6-RUNX1 Rearrangement In B-Lineage Acute Lymphoblastic Leukemia

The PAX5 gene (Paired box gene 5) works as a guardian in B-lymphopoiesis. It activates essential components of B lymphopoiesis and represses transcription of genes for differentiation to other lineage. Thus, abrogation of normal function of PAX5 is believed to contribute the leukemogenesis in B-ALL. In this study, we evaluated the utility of the detection of PAX5 gene alteration in practice in relation to PAX5 immunoexpression, other common cytogenetic changes and survival in childhood and in adult B-ALL.

Interphase FISH using PAX5 split signal probe (DakoCytomation, Glostrup, Denmark), and probes for BCR-ABL1, ETV6-RUNX1 and MLL rearrangements, and CDKN2A deletion was performed in 112 CD19+ B-ALL patients (79 children, 33 adults). G-banding and immunohistochemical staining with anti-PAX5 (BC/24, BIOCARE MEDICAL, CA, USA) antibody was also performed.

The incidence of translocation, deletion and amplification was 2.5%, 10.0% and 12.7% in children, and 0.0%, 18.2% and 6.1% in adults, respectively. Alteration of PAX5 gene was more common than BCR-ABL1 and MLL rearrangement in children (8.9% and 5.1%, respectively), and MLL rearrangement in adults (3.1%). None of the children with ETV6-RUNX1 rearrangement (22.8%) showed PAX5 gene alteration. Most cases of the deletion of PAX5 were accompanied by CDKN2A deletion. Positive immunoexpression in PAX5 IHC was observed in 74.4% in children and in 76.9% in adults Either the children with positive or negative PAX5 immunoexpression had PAX5 gene abnormalities. The presence of PAX5 gene alteration or negative immunoexpression of PAX5 did not have prognostic impact.

Based on high incidence of structural alteration of PAX5 in dominant leukemic clone, we suggest PAX5 FISH as a useful tool for the diagnosis and the disease monitoring in B-ALL. Frequent CDKN2A deletion, but not ETV6-RUNX1 rearrangement with structural alteration of PAX5 implies the role of PAX5 in determining prognosis of B-ALL. No definite relationship between the structural alteration and immunoexpression of PAX5 might be resulted from allele specific regulation and haploinsufficiency.

No relevant conflicts of interest to declare.