Genetic landscape of myelodysplastic syndrome and its prognostic relevance: a study from Pakistan.

IF 0.8 4区医学 Q3 MEDICINE, GENERAL & INTERNAL

Journal of the Pakistan Medical Association Pub Date : 2025-04-01 DOI:10.47391/JPMA.21112

Alia Waheed, Saleem Ahmed Khan, Rafia Mahmood, Hamid Saeed Malik, Humayoon Shafique Satti, Fehmida Farid Khan

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引用次数: 0

Abstract

Objective: To determine the genetic landscape of myelodysplastic syndrome patients, and to evaluate the impact of gene mutations on disease prognosis and overall survival.

Methods: This descriptive study was conducted from April 2019 to April 2021 at the Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, and comprised myelodysplastic syndrome patients of either gender. Targetted gene panel sequencing and Sanger sequencing were performed on blood and bone marrow samples. Different variant analysis was performed on sequencing data to identify the frequency of various mutations in genes related to myelodysplastic syndrome. Survival analysis and other tools were employed to analyse the impact of prognostic factors and gene mutations. Data was analysed using SPSS 24 and GraphPad Prism 8.

Results: Of the 47 patients, 32(68.1%) were males and 15(31.9%) were females. The overall median age was 66 years (interquartile range: 20 years). Targetted gene panel sequencing was done in 09(19.14%) cases, and Sanger sequencing in 38(80.85%). Mutation was present in 15(32%) cases, while it was absent in 32(68%). The most commonly mutated genes were DDX10 (9%), TET2 (6%), RUNX1(6%), and ASXL1(6%). In general, presence of any gene mutation reflected a poor prognosis (HR=1.54, p=0.24) and shorter median overall survival (median OS=7.5 months, p-trend=0.07) in MDS patients. In individual patients harbouring these mutations, the DDX10 and TET2 mutations suggested a low-risk and favourable prognosis, while RUNX1 mutations had an adverse prognosis, translating into high-risk myelodysplastic syndrome. Whereas, the ASXL1 gene exhibited both low-risk and high-risk MDS disease. In addition, SF3B1 gene mutation in MDS-MLD-RS presented with a favourable outcome. Median overall survival was 11 months (ranging from 3-38 months with an IQR of 11 months), with 36(76.6%) patients succumbing to the disease.

Conclusions: Involvement of genetic variants in the initiation, diagnosis and prognosis of myelodysplastic syndrome was noted.

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骨髓增生异常综合征的遗传景观及其预后相关性：来自巴基斯坦的一项研究。

目的：了解骨髓增生异常综合征患者的遗传格局，评价基因突变对疾病预后和总生存的影响。方法：这项描述性研究于2019年4月至2021年4月在巴基斯坦拉瓦尔品第武装部队病理研究所血液科进行，包括骨髓增生异常综合征患者，男女均可。对血液和骨髓样本进行靶基因面板测序和Sanger测序。对测序数据进行不同的变异分析，以确定与骨髓增生异常综合征相关的基因中各种突变的频率。采用生存分析等工具分析预后因素和基因突变的影响。数据分析采用SPSS 24和GraphPad Prism 8。结果：47例患者中，男性32例（68.1%），女性15例（31.9%）。总体中位年龄为66岁（四分位数范围：20岁）。靶基因面板测序09例（19.14%），Sanger测序38例（80.85%）。15例（32%）存在突变，32例（68%）不存在突变。最常见的突变基因是DDX10（9%）、TET2（6%）、RUNX1（6%）和ASXL1（6%）。一般而言，MDS患者存在任何基因突变，预后较差（HR=1.54, p=0.24），中位总生存期较短（中位OS=7.5个月，p-trend=0.07）。在携带这些突变的个体患者中，DDX10和TET2突变提示低风险和良好的预后，而RUNX1突变提示预后不良，转化为高风险骨髓增生异常综合征。然而，ASXL1基因同时表现出低风险和高风险MDS疾病。此外，SF3B1基因突变在MDS-MLD-RS中表现出良好的结果。中位总生存期为11个月（3-38个月，IQR为11个月），36例（76.6%）患者死于该疾病。结论：遗传变异参与骨髓增生异常综合征的发生、诊断和预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of the Pakistan Medical Association Medicine-General Medicine

CiteScore

1.10

自引率

11.10%

发文量

983

审稿时长

3-6 weeks

期刊介绍： Primarily being a medical journal, JPMA publishes scholarly research focusing on the various fields in the areas of health and medical education. It publishes original research describing recent advances in health particularly clinical studies, clinical trials, assessments of pathogens of diagnostic importance, medical genetics and epidemiological studies. Review articles highlighting importance of various issues in the domain of public health, drug research and medical education are also accepted. As a leading journal of South Asia, JPMA remains cognizant of the recent advances in the rapidly growing fields of biomedical sciences, it invites and encourages scholars to write short reviews and invited editorials on the emerging issues. We particularly aim to promote health standards of developing countries by encouraging manuscript submissions on issues affecting the public health and health delivery services.