费城阴性髓增殖性肿瘤（MPNs）是指造血干细胞克隆性疾病，其特征是骨髓中成熟髓系细胞的增殖和慢性炎症状态，影响恶性肿瘤的起始、进展和症状学。有三种主要实体，被定义为本质性血小板增多症（ET）、红细胞增多症（PV）和原发性骨髓纤维化（PMF），并按JAK2V617F、CALR或MPL突变进行遗传分类。在MPNs中，由于肿瘤细胞和非转化的免疫细胞产生炎性细胞因子的过度产生，慢性炎症可能会引发髓系衍生抑制细胞（MDSCs）的生成和扩张，这对适应性免疫反应具有极大的影响。虽然外周血MDSC水平升高，但MPNs患者的骨髓中的频率尚不完全清楚。我们的结果表明，所有三种类型的MPNs恶性肿瘤的骨髓和外周血液中都有CD33 + HLA-DR- /低表型的总（T）-MDSC和多形核（PMN）-MDSC级别升高。然而，这些骨髓MDSC频率的增加与临床参数（如肝大，白细胞，血红蛋白或血小板水平）或JAK2和CALR突变没有相关性。此外，来自ET、PV和PMF患者的骨髓MDSC表现出免疫抑制功能，确定为T细胞增殖抑制。值得注意的是，PMF样品中发现了最高的T-MDSC和PMN-MDSC水平，并且MDSC频率的增加与骨髓纤维化程度密切相关。因此，这些数据共同表明，免疫抑制的MDSC人群在MPNs患者的骨髓中增加，并可能涉及形成纤维化微环境。© 2023年。作者（经Springer Nature Switzerland AG独家许可）

The Philadelphia-negative myeloproliferative neoplasms (MPNs), defined as clonal disorders of the hematopoietic stem cells, are characterized by the proliferation of mature myeloid cells in the bone marrow and a chronic inflammatory status impacting the initiation, progression, and symptomatology of the malignancies. There are three main entities defined as essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), and genetically classified by JAK2V617F, CALR, or MPL mutations. In MPNs, due to the overproduction of inflammatory cytokines by the neoplastic cells and non-transformed immune cells, chronic inflammation may provoke the generation and expansion of myeloid-derived suppressors cells (MDSCs) that highly influence the adaptive immune response. Although peripheral blood MDSC levels are elevated, their frequency in the bone marrow of MPNs patients is not well elucidated yet. Our results indicated increased levels of total (T)-MDSCs (CD33+HLA-DR-/low) and polymorphonuclear (PMN)-MDSCs (CD33+/HLA-DRlow/CD15+/CD14-) in the bone marrow and peripheral blood of all three types of MPNs malignancies. However, these bone marrow MDSCs-increased frequencies did not correlate with the clinical parameters, such as hepatomegaly, leukocytes, hemoglobin, or platelet levels, or with JAK2 and CALR mutations. Besides, bone marrow MDSCs, from ET, PV, and PMF patients, exhibited immunosuppressive function, determined as T-cell proliferation inhibition. Notably, the highest T-MDSCs and PMN-MDSC levels were found in PMF samples, and the increased MDSCs frequency strongly correlated with the degree of myelofibrosis. Thus, these data together indicate that the immunosuppressive MDSCs population is increased in the bone marrow of MPNs patients and may be implicated in generating a fibrotic microenvironment.© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.