原发性血小板增多症 (ET) 和前纤维化原发性骨髓纤维化 (pre-PMF) 是费城染色体阴性骨髓增殖性肿瘤。这些病症具有重叠的临床表现；然而，他们的预后却截然不同。目前的形态学诊断方法在亚型区分方面缺乏可靠性，这凸显了改进诊断的必要性。本研究的目的是调查 ET 和 PMF 患者骨髓活检中的多组学变化，以提高我们对这两种疾病的细微诊断特征的理解。我们通过 4D 直接数据独立采集进行蛋白质组分析，并通过 2bRAD-M 测序技术进行微生物组分析，以确定未经治疗的 ET 患者和 PMF 前患者之间的差异蛋白质和微生物水平。在 ET 和 PMF 之前观察到实验室和多组学差异，涵盖不同的途径，例如脂质代谢和免疫反应。 PMF前组表现出中性粒细胞与淋巴细胞的比率增加以及高密度脂蛋白和胆固醇水平降低。蛋白质分析显示，PMF 前的 CXCR2、CXCR4 和 MX1 水平显着升高，而 ET 中的 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 PMF 前的分枝杆菌、黄杆菌和 L1I39 水平升高，而鞘氨醇单胞菌、短杆菌和假单胞菌_E 显着降低，这些属的 AUC 范围为 0.833 至 0.929。我们的研究提供了对 ET 和 PMF 患者骨髓中蛋白质组和微生物组变化的初步见解，确定了需要进一步研究作为潜在诊断指标的特定蛋白质和细菌属。这些观察结果有助于我们不断加深对 ET 和 pre-PMF 背后的多组学变异和可能机制的理解。© 2024。作者。

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.© 2024. The Author(s).