体细胞 FANCD2 突变(c.2022-5C>T)作为慢性粒细胞白血病早期疾病进展的新型分子生物标记物的临床验证:病例对照研究

IF 1.1 Q4 HEMATOLOGY Hematology Reports Pub Date : 2024-07-08 DOI:10.3390/hematolrep16030045
N. Alanazi, Abdulaziz Siyal, S. Basit, Masood Shammas, S. AlMukhaylid, A. Aleem, Amer Mahmood, Zafar Iqbal
{"title":"体细胞 FANCD2 突变(c.2022-5C>T)作为慢性粒细胞白血病早期疾病进展的新型分子生物标记物的临床验证:病例对照研究","authors":"N. Alanazi, Abdulaziz Siyal, S. Basit, Masood Shammas, S. AlMukhaylid, A. Aleem, Amer Mahmood, Zafar Iqbal","doi":"10.3390/hematolrep16030045","DOIUrl":null,"url":null,"abstract":"Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients’ blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical Validation of the Somatic FANCD2 Mutation (c.2022-5C>T) as a Novel Molecular Biomarker for Early Disease Progression in Chronic Myeloid Leukemia: A Case–Control Study\",\"authors\":\"N. Alanazi, Abdulaziz Siyal, S. Basit, Masood Shammas, S. AlMukhaylid, A. Aleem, Amer Mahmood, Zafar Iqbal\",\"doi\":\"10.3390/hematolrep16030045\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients’ blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials.\",\"PeriodicalId\":12829,\"journal\":{\"name\":\"Hematology Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2024-07-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematology Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/hematolrep16030045\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematology Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/hematolrep16030045","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:慢性髓性白血病(CML)是由染色体易位t(9;22)导致BCR-ABL融合癌基因形成的。CML分为三个阶段:慢性期(CP)、加速期(AP)和爆发期(BC)。酪氨酸激酶抑制剂(TKIs)彻底改变了 CML 的治疗方法。酪氨酸激酶抑制剂在 CP-CML 中疗效显著,这些患者的存活率与正常人群相似,但酪氨酸激酶抑制剂对晚期 CML 的疗效较差。即使目前的治疗取得了进展,BC-CML 患者的平均总生存期也不到一年。早期识别有疾病进展风险的 CML 患者有助于及时使用适当的 TKIs 或其他治疗方法进行干预。虽然有一些疾病进展的标志物,如 BCR-ABL 激酶域、ASXL1 和 GATA2 突变,但目前还没有通用的、专门的特异性分子生物标志物来早期诊断有 CML 进展风险的 CML 患者,以便及时采取治疗干预措施,延缓或尽量减少 CML 的爆破危象转化。最近的一项研究发现,所有 BC-CML 患者都携带 FANCD2(c.2022-5C>T)突变。因此,本研究旨在检测 AP-CML(早期进展期)中的 FANCD2 突变,并在临床上验证其作为 CML 早期从 CP 进展到 AP 的新型分子生物标记物的潜力。研究方法我们的研究包括来自 2 个肿瘤中心的 123 名 CP-CML(对照组)和 60 名 AP-CML 患者(实验组),研究时间为 2020 年 1 月至 2023 年 7 月。AP-CML 患者的平均血红蛋白水平、白细胞计数、血小板计数、治疗类型、肝肿大、脾肿大和生存状况与 CP-CML 患者有显著差异。然而,由于这些临床参数无法帮助早期发现有CML进展风险的患者,因此需要一种经临床验证的AP-CML生物标志物。研究人员从患者的血液样本中提取了 DNA,并使用 Illumina NextSeq500 下一代测序仪(NGS)对 FANCD2 基因进行了测序。结果显示NGS 分析发现 FANCD2 基因中存在一个独特的剪接位点突变(c.2022-5C>T)。大多数 AP-CML 患者(98.3%)都检测到了这一突变,但 CP-CML 患者或基因组数据库中的健康对照序列均未检测到这一突变。该突变通过桑格测序得到证实。FANCD2 是范可尼贫血症通路基因的一个成员,参与 DNA 修复和基因组稳定性,该基因的畸变与许多癌症有关。结论总之,我们的研究表明,体细胞 FANCD2(c.2022-5C>T)突变是 CML 早期进展的新分子生物标志物。我们建议在前瞻性临床试验中进一步对该生物标志物进行临床验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Clinical Validation of the Somatic FANCD2 Mutation (c.2022-5C>T) as a Novel Molecular Biomarker for Early Disease Progression in Chronic Myeloid Leukemia: A Case–Control Study
Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients’ blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Hematology Reports
Hematology Reports HEMATOLOGY-
CiteScore
0.90
自引率
0.00%
发文量
47
审稿时长
10 weeks
期刊最新文献
Gene Therapy: A Revolutionary Step in Treating Thalassemia. Pancytopenia Related to Splenic Angiosarcoma: A Case Report and Literature Review. Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia: Results of a Single-Center Study. Trabecular Attenuation of L1 in Adult Patients with Multiple Myeloma: An Observational Study on Low-Dose CT Images. Utilizing Clinical Transformation Criteria for Prognostic Stratification in Follicular Lymphoma Prior to Initial Immunochemotherapy.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1