High frequency of IKZF1 genetic alterations in adult patients with B-cell acute lymphoblastic leukemia

Alterations in the IKZF1 gene are associated with poor prognosis in pediatric B-cell acute lymphoblastic leukemia (B-ALL). We examined the relationship between IKZF1 alterations and clinical findings in 78 adult patients with B-ALL. Aberrant isoforms of IKZF1 were detected using RT-PCR. The copy numbers of IKZF1 exons and fusion genes caused by exon deletions were determined using RQ-PCR and genomic PCR, respectively. We detected aberrant IKZF1 isoforms in 20 of the 78 patients (13 Ik6 and seven Ik10) and deletions of the entire or parts of the IKZF1 gene in 40 of 70 patients. No IKZF1 point mutations were detected by direct sequencing. Nineteen Ik6 and Ik10 isoforms had been generated through genomic exon deletions, but one through aberrant splicing. In total, 41 of the 78 (52.6%) patients harbored IKZF1 alterations, which were identified in 20 of 24 (83.3%) patients with Philadelphia chromosome (Ph)-positive B-ALL compared with 21 of 54 (38.9%) Ph-negative B-ALL (P = 0.0004). IKZF1 alterations are highly involved even in adults with B-ALL. To fully detect IKZF1 alterations, several methods with alternative approaches are required. To elucidate the clinical significance of IKZF1 alterations in adult B-ALL, our study warrants prospective clinical studies with a full analysis of IKZF1 alterations.