PDF(Pubmed)
Abstract：
Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms. These conditions share overlapping clinical presentations; however, their prognoses differ significantly. Current morphological diagnostic methods lack reliability in subtype differentiation, underlining the need for improved diagnostics. The aim of this study was to investigate the multi-omics alterations in bone marrow biopsies of patients with ET and pre-PMF to improve our understanding of the nuanced diagnostic characteristics of both diseases. We performed proteomic analysis with 4D direct data-independent acquisition and microbiome analysis with 2bRAD-M sequencing technology to identify differential protein and microbe levels between untreated patients with ET and pre-PMF. Laboratory and multi-omics differences were observed between ET and pre-PMF, encompassing diverse pathways, such as lipid metabolism and immune response. The pre-PMF group showed an increased neutrophil-to-lymphocyte ratio and decreased high-density lipoprotein and cholesterol levels. Protein analysis revealed significantly higher CXCR2, CXCR4, and MX1 levels in pre-PMF, while APOC3, APOA4, FABP4, C5, and CFB levels were elevated in ET, with diagnostic accuracy indicated by AUC values ranging from 0.786 to 0.881. Microbiome assessment identified increased levels of Mycobacterium, Xanthobacter, and L1I39 in pre-PMF, whereas Sphingomonas, Brevibacillus, and Pseudomonas_E were significantly decreased, with AUCs for these genera ranging from 0.833 to 0.929. Our study provides preliminary insights into the proteomic and microbiome variations in the bone marrow of patients with ET and pre-PMF, identifying specific proteins and bacterial genera that warrant further investigation as potential diagnostic indicators. These observations contribute to our evolving understanding of the multi-omics variations and possible mechanisms underlying ET and pre-PMF.
摘要：
原发性血小板增多症（ET）和纤维化前原发性骨髓纤维化（pre-PMF）是费城染色体阴性的骨髓增殖性肿瘤。这些情况具有重叠的临床表现；然而，他们的预后差异很大。目前的形态学诊断方法在亚型分化中缺乏可靠性，强调需要改进诊断。这项研究的目的是研究ET和PMF前患者骨髓活检中的多组学改变，以提高我们对这两种疾病的细微差别诊断特征的理解。我们使用4D直接数据无关采集进行蛋白质组学分析，并使用2bRAD-M测序技术进行微生物组分析，以鉴定未经治疗的ET患者和PMF前患者之间的差异蛋白质和微生物水平。观察到ET和pre-PMF之间的实验室和多组学差异，包含不同的途径，如脂代谢和免疫反应。前PMF组显示中性粒细胞与淋巴细胞的比率增加，高密度脂蛋白和胆固醇水平降低。蛋白质分析显示，pre-PMF中CXCR2、CXCR4和MX1水平显著升高，而ET中APOC3、APOA4、FABP4、C5和CFB水平升高，AUC值范围为0.786至0.881，表明诊断准确性。微生物组评估发现分枝杆菌水平升高，黄杆菌属,和Pre-PMF中的L1I39，而鞘氨醇单胞菌，短芽孢杆菌,假单胞菌E明显减少，这些属的AUC范围从0.833到0.929。我们的研究提供了对ET和pre-PMF患者骨髓中蛋白质组和微生物组变化的初步见解。鉴定需要进一步研究的特定蛋白质和细菌属作为潜在诊断指标。这些观察结果有助于我们对多组学变化以及ET和PMF之前的可能机制的不断发展的理解。
