南非BCR/ABL阴性MPN患者JAK2/STAT5通路突变频率

Q1 Medicine
Karen L Shires, Adriana J Rust, Rushil Harryparsad, Justin A Coburn, Ruth E Gopie
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引用次数: 2

摘要

背景:JAK2/STAT5增殖通路基因突变是骨髓增生性肿瘤(MPNBCR/ABLneg)诊断的关键,在50-97%的MPNBCR/ABLneg亚型中发现JAK2V617F。低JAK2V617F阳性表明南非MPNBCR/ABLneg人群可能具有不同的突变景观。目的:我们旨在确定与我们当地MPNBCR/ABLneg人群相关的JAK2/STAT5突变频率,从而确定这些分子检测在该组中的相关性。我们还调查了每个测试要求的血液病理学相关性,以评估测试实践。方法:本研究对886例因疑似MPN诊断而要求进行JAK2V617F突变检测的患者进行回顾性审计。采用FBC指数、促红细胞生成素水平和骨髓活检结果对患者进行分类。检测JAK2V617F阴性患者DNA钙网蛋白(CALR)外显子9、骨髓增殖性白血病蛋白(MPL)密码子515和JAK2外显子12突变。结果:只有23%的患者表现出JAK2V617F阳性,另外还有29例CALR/MPL突变被检测到。正如预期的那样,突变仅在FBC指数异常的患者中检测到,但37%的检测请求与检测时的异常参数无关。突变频率如下:真性多红细胞血症:97% JAK2V617F/3% (JAK2、CALR、MPL)三阴性;原发性血小板增多症:72% JAK2V617F/23%CALR/5%三阴性;原发性髓纤维化:78%JAK2V617F/16%CALR/6%三阴性。结论:我们的研究表明,我们的MPNBCR/ABLneg患者与其他MPN人群具有相似的遗传景观,>93%的患者能够通过单独检测JAK2V617F和CALR外显子9突变来诊断。建议采用世卫组织2016年指南来指导检测做法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
JAK2/STAT5 Pathway Mutation Frequencies in South African BCR/ABL Negative MPN Patients.

Background: Mutations in JAK2/STAT5 proliferation pathway genes are key in the diagnosis of myeloproliferative neoplasms (MPNBCR/ABLneg), with JAK2V617F being found in 50-97% of MPNBCR/ABLneg subtypes. Low JAK2V617F positivity at our facility suggested that our South African MPNBCR/ABLneg population may have a different mutational landscape.

Objectives: We aimed to determine the JAK2/STAT5 mutation frequencies associated with our local MPNBCR/ABLneg population, thus determining the relevance of these molecular tests in this group. We also investigated the haematopathological relevance of each test request, to assess testing practises.

Method: This study involved the retrospective audit of 886 patients for whom JAK2V617F mutation testing had been requested for a suspected MPN diagnosis. FBC indices, erythropoietin levels and bone marrow biopsy results were used to classify the patients. JAK2V617F negative patient DNA was tested for calreticulin (CALR) exon9, myeloproliferative leukaemia protein (MPL) codon515 and JAK2 exon12 mutations.

Results: Only 23% of the patients demonstrated JAK2V617F positivity, with an additional 29 cases of CALR/MPL mutations being detected. Mutations were only detected in patients with abnormal FBC indices, as expected, yet 37% of the test requests were not associated with abnormal parameters at the time of testing. Mutation frequencies were as follows: Polycythaemia Vera: 97% JAK2V617F/3% (JAK2, CALR, MPL) triple negative; Essential thrombocythemia: 72% JAK2V617F/23%CALR/5%triple negative; Primary Myelofibrosis: 78%JAK2V617F/16%CALR/6%triple negative.

Conclusion: Our study demonstrated that our MPNBCR/ABLneg patients have a similar genetic landscape to other MPN populations, with >93% being able to be diagnosed by testing for the JAK2V617F and CALR exon9 mutations alone. Adoption of the WHO 2016 guidelines is recommended to guide testing practices.

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来源期刊
CiteScore
4.30
自引率
0.00%
发文量
0
审稿时长
27 weeks
期刊介绍: Hematology Oncology and Stem Cell Therapy is an international, peer-reviewed, open access journal that provides a vehicle for publications of high-quality clinical as well as basic science research reports in hematology and oncology. The contents of the journal also emphasize the growing importance of hematopoietic stem cell therapy for treatment of various benign and malignant hematologic disorders and certain solid tumors.The journal prioritizes publication of original research articles but also would give consideration for brief reports, review articles, special communications, and unique case reports. It also offers a special section for clinically relevant images that provide an important educational value.
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