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基于免疫球蛋白基因重排的突尼斯B细胞急性淋巴细胞白血病微小残留病检测

Minimal residual disease detection in Tunisian B-acute lymphoblastic leukemia based on immunoglobulin gene rearrangements.

作者信息

Besbes S, Hamadou W S, Boulland M L, Youssef Y B, Achour B, Regaieg H, Khelif A, Fest T, Soua Z

机构信息

Research Unit 14 ES 19, Department of Biochemistry, Faculty of Medicine, University of Sousse, Sousse, Tunisia.

Biological Hematology Department, Centre Hospitalier Universitaire Pontchaillou, Rennes, France.

出版信息

Braz J Med Biol Res. 2017 Jan 16;50(1):e5426. doi: 10.1590/1414-431X20165426.

Abstract

IGH gene rearrangement and IGK-Kde gene deletion can be used as molecular markers for the assessment of B lineage acute lymphoblastic leukemia (B-ALL). Minimal residual disease detected based on those markers is currently the most reliable prognosis factor in B-ALL. The aim of this study was to use clonal IGH/IGK-Kde gene rearrangements to confirm B-ALL diagnosis and to evaluate the treatment outcome of Tunisian leukemic patients by monitoring the minimal residual disease (MRD) after induction chemotherapy. Seventeen consecutive newly diagnosed B-ALL patients were investigated by multiplex PCR assay and real time quantitative PCR according to BIOMED 2 conditions. The vast majority of clonal VH-JH rearrangements included VH3 gene. For IGK deletion, clonal VK1f/6-Kde recombinations were mainly identified. These rearrangements were quantified to follow-up seven B-ALL after induction using patient-specific ASO. Four patients had an undetectable level of MRD with a sensitivity of up to 10-5. This molecular approach allowed identification of prognosis risk group and adequate therapeutic decision. The IGK-Kde and IGH gene rearrangements might be used for diagnosis and MRD monitoring of B-ALL, introduced for the first time in Tunisian laboratories.

摘要

IGH基因重排和IGK-Kde基因缺失可作为评估B淋巴细胞白血病(B-ALL)的分子标志物。基于这些标志物检测到的微小残留病是目前B-ALL中最可靠的预后因素。本研究的目的是利用克隆性IGH/IGK-Kde基因重排来确诊B-ALL,并通过监测诱导化疗后的微小残留病(MRD)来评估突尼斯白血病患者的治疗结果。根据BIOMED 2条件,采用多重PCR检测和实时定量PCR对17例连续新诊断的B-ALL患者进行研究。绝大多数克隆性VH-JH重排包含VH3基因。对于IGK缺失,主要鉴定出克隆性VK1f/6-Kde重组。使用患者特异性ASO对这些重排进行定量,以随访7例诱导后的B-ALL。4例患者的MRD水平检测不到,灵敏度高达10-5。这种分子方法有助于识别预后风险组并做出适当的治疗决策。IGK-Kde和IGH基因重排可用于B-ALL的诊断和MRD监测,这是首次在突尼斯实验室引入。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d130/5264541/85c5a36d629d/1414-431X-bjmbr-1414-431X20165426-gf01.jpg

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