巴基斯坦患者骨髓增殖性肿瘤的体细胞突变景观

IF 1.8 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy Pub Date : 2025-07-01 DOI:10.1016/j.htct.2025.103901

Mehreen Ali Khan

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引用次数: 0

摘要

目的：本研究旨在筛选骨髓增生性肿瘤（MPN）患者在临床和骨髓检查后的四种已知基因突变，以确定治疗前的诊断。方法本描述性横断面研究于2018年1月至2021年1月在拉瓦尔品第武装部队骨髓移植中心进行。共纳入159例符合纳入标准的MPN患者。所有患者均在知情同意、病史记录和检查后行骨髓活检。外周血样本筛选JAK2 V617F、JAK2 12外显子、CALR和cMPL基因的体细胞突变。采用常规PCR对JAK2 V617F和cMPL突变进行分析，并对PCR产物进行聚丙烯酰胺凝胶电泳分析。利用片段分析技术分析JAK2 12外显子和CALR突变。每个样品进行阳性对照和阴性对照。使用Gene Mapper 5软件（Applied Biosystems）对最终结果进行分析。基因扫描数据通过分析电泳图和基因分型数据表进行解释。使用社会科学统计软件包（SPSS） 25.0版对数据进行分析。结果159例MPN患者符合纳入标准，其中男性104例（65.4%），女性55例（34.6%）。患者年龄中位数为54岁（IQR: 38-64）。在费城阴性（Ph-ive） MPN患者中，69例（43.4%）诊断为原发性骨髓纤维化（PMF）， 60例（37.7%）诊断为真性红细胞增多症（PV）， 30例（18.9%）诊断为原发性血小板增多症（ET）。JAK2 V617F在PV、ET和PMF患者中的突变频率分别为85%、51.4%和34.5%。仅在1例PMF和5例ET患者（17.2%）中观察到CALR突变。此外，在我们的患者中未发现cMPL突变。然而，14例（8.8%）患者为三阴性（JAK2 V617F、CALR和cMPL突变阴性）。结论ph - 5型MPN患者以spmf为主（43.4%），其次为PV 60（37.7%）和ET 30（18.9%）。JAK2 V617F在PV、ET和PMF患者中的突变频率分别为85%、51.4%和34.5%。仅在5例ET（17.2%）和1例PMF患者中观察到CALR突变。这五种突变是世界卫生组织制定的诊断标准之一，可以快速可靠地诊断MPN。结论：本研究强调了来自低收入国家的MPN患者的人口统计学、诊断和四种基因突变。在ph - 5 MPN患者中，PMF最为常见（43.4%），其次是PV 60（37.7%）和ET 30（18.9%）。JAK2 V617F在PV、ET和PMF患者中的突变频率分别为85%、51.4%和34.5%。仅在1例PMF和5例ET患者（17.2%）中观察到CALR突变。这五种突变是世卫组织为快速可靠地诊断MPN而制定的诊断标准之一。考虑到需要与来自多中心的更大的队列进行进一步研究，可以包括少数系。使用高通量测序技术鉴定这些基因中其他任何位置的突变，不应该是4个吗？

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LANDSCAPE OF SOMATIC MUTATIONS OF MYELOPROLIFERATIVE NEOPLASMS IN PAKISTANI PATIENTS

Objective

This study aimed to screen Myeloproliferative Neoplasm (MPN) patients for four known genetic mutations following their clinical and bone marrow examinations to establish a diagnosis before treatment.

Methods

This descriptive cross-sectional study was conducted at the Armed forces bone marrow transplant center, Rawalpindi, between January 2018 and January 2021. A total of 159 MPN patients who fulfilled inclusion criteria were enrolled. All patients underwent bone marrow biopsy after providing informed consent, history recording, and examination. Peripheral blood samples were screened for somatic mutations in JAK2 V617F, JAK2 exon 12, CALR, and cMPL genes. The JAK2 V617F and cMPL mutations were analyzed using conventional PCR, and the PCR products were analyzed on polyacrylamide gel electrophoresis. JAK2 Exon 12 and CALR mutations were analyzed using the fragment analysis technique. Positive and negative controls were run with each sample. The final results were analyzed using Gene Mapper 5 Software (Applied Biosystems). The gene scan data was interpreted by analyzing the electropherograms and the genotyping data sheet. The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 25.0.

Results

A total of 159 MPN patients fulfilled the inclusion criteria, with 104 (65.4%) males and 55 (34.6%) females. The median age of patients was 54-years (IQR: 38‒64). Among Philadelphia negative (Ph-ive) MPN patients, 69 (43.4%) were diagnosed with Primary Myelofibrosis (PMF), 60 (37.7%) as Polycythemia Vera (PV), and 30 (18.9%) as Essential Thrombocytosis (ET). The frequency of the JAK2 V617F mutation in PV, ET, and PMF patients was 85%, 51.4%, and 34.5%, respectively. CALR mutation was observed only in 1 PMF and 5 (17.2%) ET patients. Additionally, cMPL mutation was not found among our patients. However, 14 (8.8%) patients were triple negative (negative for the JAK2 V617F, CALR, and cMPL mutations).

Conclusions

PMF was the most frequent (43.4%) condition among Ph-ive MPN patients, followed by PV 60 (37.7%) and ET 30 (18.9%). The frequency of JAK2 V617F mutation in PV, ET, and PMF patients was 85%, 51.4%, and 34.5%, respectively. CALR mutation was observed only in 5 (17.2%) ET and 1 PMF patient. These five mutations are among the diagnostic criteria established by the World Health Organization, which enable a quick and reliable diagnosis of MPN.

Conclusion

This study highlights the demographics, diagnosis, and mutations in four genes of MPN patients from a low-income country. PMF was the most frequent (43.4%) among Ph-ive MPN patients, followed by PV 60 (37.7%) and ET 30 (18.9%). The frequency of the JAK2 V617F mutation in PV, ET, and PMF patients was 85%, 51.4%, and 34.5%, respectively. CALR mutation was observed in only 1 PMF and 5 (17.2%) ET patients. These five mutations are among the diagnostic criteria established by WHO for a quick and reliable diagnosis of MPN. Few lines can be included regarding the need of further studies with larger cohort from multi centers Use of high throughput sequencing techniques for identifying mutations located anywhere else in these genes Shouldn’t it be 4?

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