Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia

被引：6

作者：

Hashiguchi, Junichi ^{[1
]}

Onozawa, Masahiro ^{[1
]}

Oguri, Satoshi ^{[2
]}

Fujisawa, Shinichi ^{[2
]}

Tsuji, Masahisa ^{[3
]}

Okada, Kohei ^{[1
]}

Nakagawa, Masao ^{[1
]}

Hashimoto, Daigo ^{[1
]}

Kahata, Kaoru ^{[1
]}

Kondo, Takeshi ^{[1
]}

Shimizu, Chikara ^{[2
]}

Teshima, Takanori ^{[1
]}

机构：

[1] Hokkaido Univ, Fac Med, Grad Sch Med, Dept Hematol, Sapporo, Hokkaido, Japan

[2] Hokkaido Univ Hosp, Div Lab & Transfus Med, Sapporo, Hokkaido, Japan

[3] Chromosome Sci Lab, Sapporo, Hokkaido, Japan

来源：

JOURNAL OF MOLECULAR DIAGNOSTICS | 2018年 / 20卷 / 04期

基金：

日本学术振兴会;

关键词：

ILLEGITIMATE V(D)J RECOMBINATION; PROGNOSIS; IKAROS; GENE; ANTIBODIES; ANTIGENS; FREQUENT;

D O I：

10.1016/j.jmoldx.2018.02.005

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Intragenic deletion of IKZF1 is a recurrent genomic alteration in acute lymphoblastic leukemia. The deletions are mediated by illegitimate variable(diversity)joining recombination via cryptic recombination signal sequences (RSSs). We developed a fluorescence in situ hybridization (FISH) probe set that can detect any type of IKZF1 deletion, including the commonly deleted exon 4 to 7 region. The probe set consists of a designed probe for the commonly deleted region (Cy3; red) and a bacterial artificial chromosomes clone probe for detecting the 3' flanking region (Spectrum Green). Intact IKZF1 showed a fusion signal, and the deleted allele showed loss of the red signal (0R1G1F). The FISH probes worked correctly for human leukemic cell lines and clinical samples. One case showed an atypical break-apart signal (1R1G1F). Inverse PCR of the case revealed rearrangement of the excised IKZF1 fragment into a legitimate RSS site at Ig kappa on chromosome 2, suggesting a pathogenic role of this recombination-activating gene 1/2-mediated event. In this study, we established FISH probe detecting IKZF1 deletion in a quick, quantitative, and cost-effective manner, and the results provided a novel insight into B-cell receptor editing by rearrangement of a cryptic RSS-mediated genomic fragment in acute lymphoblastic leukemia pathology.

引用

页码：446 / 454

页数：9

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