骨髓增生性肿瘤（MPN）的特点是髓系细胞的不可控扩增，与某些驱动基因中的疾病相关突变（包括JAK2、CALR和MPL），以及转化为二级急性髓细胞白血病（sAML）的相当大的危险性。虽然表现为干细胞肿瘤，但关于MPN中疾病启动干细胞的了解很少。我们建立了推测的CD34+ /CD38-干细胞和CD34+ /CD38+祖细胞的表型。共检查了111名患有红细胞增多症、 Essential Thrombocythemia 或原发性骨髓纤维化（PMF）的MPN患者。在几乎所有接受检测的患者中，CD34+ /CD38-干细胞表达CD33、CD44、CD47、CD52、CD97、CD99、CD105、CD117、CD123、CD133、CD184、CD243和CD274（PD-L1）。在PMF患者中，MPN干细胞通常以异常的方式表达CD25，并且有时也会表达CD26。MPN干细胞未表现出大量的CD90、CD273（PD-L2）、CD279（PD-1）、CD366（TIM-3）、CD371（CLL-1）或IL-1RAP。CD34+ /CD38-干细胞的表型在MPN进展到sAML期间没有显著变化。在NSGS小鼠中，推测的MPN干细胞的疾病启动能力得到了确认。虽然CD34+ /CD38- MPN细胞在NSGS小鼠中植入，但是CD34+ /CD38+或CD34-细胞并没有产生实质性植入。针对JAK2的药物fedratinib和BRD4降解剂dBET6诱导了MPN干细胞的凋亡并抑制了增殖。因此，MPN干细胞显示出独特的表型，包括细胞因子受体、免疫检查点分子和其他临床相关的靶抗原。MPN和sAML中肿瘤性干细胞的表型特征应该有助于它们的富集和更好的干细胞根除（治愈）疗法的开发。本文受版权保护。版权所有。

Myeloproliferative neoplasms (MPN) are characterized by uncontrolled expansion of myeloid cells, disease-related mutations in certain driver-genes including JAK2, CALR and MPL, and a substantial risk to progress to secondary acute myeloid leukemia (sAML). Although behaving as stem cell neoplasms, little is known about disease-initiating stem cells in MPN. We established the phenotype of putative CD34+ /CD38- stem cells and CD34+ /CD38+ progenitor cells. A total of 111 patients with MPN suffering from polycythemia vera, essential thrombocythemia, or primary myelofibrosis (PMF) were examined. In almost all patients tested, CD34+ /CD38- stem cells expressed CD33, CD44, CD47, CD52, CD97, CD99, CD105, CD117, CD123, CD133, CD184, CD243, and CD274 (PD-L1). In patients with PMF, MPN stem cells often expressed CD25 and sometimes also CD26 in an aberrant manner. MPN stem cells did not exhibit substantial amounts of CD90, CD273 (PD-L2), CD279 (PD-1), CD366 (TIM-3), CD371 (CLL-1), or IL-1RAP. The phenotype of CD34+ /CD38- stem cells did not change profoundly during progression from MPN to sAML. The disease-initiating capacity of putative MPN stem cells was confirmed in NSGS mice. Whereas CD34+ /CD38- MPN cells engrafted in NSGS mice, no substantial engraftment was produced by CD34+ /CD38+ or CD34- cells. The JAK2-targeting drug fedratinib and the BRD4 degrader dBET6 induced apoptosis and suppressed proliferation in MPN stem cells. Together, MPN stem cells display a unique phenotype, including cytokine receptors, immune checkpoint molecules and other clinically relevant target antigens. Phenotypic characterization of neoplastic stem cells in MPN and sAML should facilitate their enrichment and the development of better, stem cell-eradicating (curative), therapies. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.