Helmholtz Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany.
Institute for Biomedical Engineering-Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
PLoS One. 2018 May 31;13(5):e0197233. doi: 10.1371/journal.pone.0197233. eCollection 2018.
Myeloproliferative neoplasms (MPN)-such as polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF)-are typically diseases of the elderly caused by acquired somatic mutations. However, it is largely unknown how the malignant clone interferes with normal hematopoiesis. In this study, we analyzed if serum of MPN patients comprises soluble factors that impact on hematopoietic stem and progenitor cells (HPCs).
CD34+ HPCs were cultured in medium supplemented with serum samples of PV, ET, or MF patients, or healthy controls. The impact on proliferation, maintenance of immature hematopoietic surface markers, and colony forming unit (CFU) potential was systematically analyzed. In addition, we compared serum of healthy young (<25 years) and elderly donors (>50 years) to determine how normal aging impacts on the hematopoiesis-supportive function of serum.
Serum from MF, PV and ET patients significantly increased proliferation as compared to controls. In addition, serum from MF and ET patients attenuated the loss of a primitive immunophenotype during in vitro culture. The CFU counts were significantly higher if HPCs were cultured with serum of MPN patients as compared to controls. Furthermore, serum of healthy young versus old donors did not evoke significant differences in proliferation or immunophenotype of HPCs, whereas the CFU frequency was significantly increased by serum from elderly patients.
Our results indicate that serum derived from patients with MPN comprises activating feedback signals that stimulate the HPCs-and this stimulatory signal may result in a viscous circle that further accelerates development of the disease.
骨髓增殖性肿瘤（MPN）-如真性红细胞增多症（PV）、特发性血小板增多症（ET）和骨髓纤维化（MF）-通常是由获得性体细胞突变引起的老年疾病。然而，恶性克隆如何干扰正常造血在很大程度上尚不清楚。在这项研究中，我们分析了 MPN 患者的血清中是否包含影响造血干细胞和祖细胞（HPC）的可溶性因子。
将 CD34+HPC 在补充有 PV、ET 或 MF 患者或健康对照者血清的培养基中培养。系统分析对增殖、幼稚造血表面标志物的维持和集落形成单位（CFU）潜能的影响。此外，我们比较了健康年轻（<25 岁）和老年（>50 岁）供体的血清，以确定正常衰老如何影响血清对造血的支持功能。
与对照组相比，MF、PV 和 ET 患者的血清显著增加了增殖。此外，MF 和 ET 患者的血清减轻了体外培养过程中原始免疫表型的丧失。与对照组相比，如果用 MPN 患者的血清培养 HPC，则 CFU 计数明显更高。此外，与年轻供体（<25 岁）相比，健康老年供体的血清在 HPC 的增殖或免疫表型方面没有引起明显差异，而老年患者的血清使 CFU 频率显著增加。
我们的研究结果表明，来自 MPN 患者的血清包含激活反馈信号，刺激 HPC-并且这种刺激信号可能导致一个粘性循环，进一步加速疾病的发展。
