High frequency of IKZF1 genetic alterations in adult patients with B‐cell acute lymphoblastic leukemia. (7th July 2013)

• Record Type: Journal Article
• Authors: Tokunaga, Kenji; Yamaguchi, Shunichiro; Iwanaga, Eisaku; Nanri, Tomoko; Shimomura, Taizo; Suzushima, Hitoshi; Mitsuya, Hiroaki; Asou, Norio
• Is Part Of: European journal of haematology. Volume 91:Number 3(2013:Sep.)
• Page Start: 201
• Page End: 208
• Publication Date: 2013-07-07
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.12155
• Languages: English
• ISSNs: 0902-4441

Abstract

<abstract abstract-type="main" id="ejh12155-abs-0001"> <title>Abstract</title> <p>Alterations in the <italic>IKZF1</italic> gene are associated with poor prognosis in pediatric B‐cell acute lymphoblastic leukemia (B‐ALL). We examined the relationship between <italic>IKZF1</italic> alterations and clinical findings in 78 adult patients with B‐ALL. Aberrant isoforms of <italic>IKZF1</italic> were detected using RT‐PCR. The copy numbers of <italic>IKZF1</italic> exons and fusion genes caused by exon deletions were determined using RQ‐PCR and genomic PCR, respectively. We detected aberrant <italic>IKZF1</italic> isoforms in 20 of the 78 patients (13 Ik6 and seven Ik10) and deletions of the entire or parts of the <italic>IKZF1</italic> gene in 40 of 70 patients. No <italic>IKZF1</italic> 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 <italic>IKZF1</italic> 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 (<italic>P </italic>=<italic> </italic>0.0004). <italic>IKZF1</italic> alterations are highly involved even in adults with B‐ALL. To fully detect <italic>IKZF1</italic> alterations, several methods with alternative approaches are required. To elucidate the clinical significance of <italic>IKZF1</italic> alterations in adult B‐ALL, our study warrants prospective clinical studies with a full analysis of <italic>IKZF1</italic> alterations.</p> </abstract>