Wang Jen Chin, Kundra Ajay, Andrei Mirela, Baptiste Stacey, Chen Chi, Wong Ching, Sindhu Hemant
Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
Leuk Res. 2016 Apr;43:39-43. doi: 10.1016/j.leukres.2016.02.004. Epub 2016 Feb 16.
Although BCR-ABL negative myeloproliferative neoplasms (MPN)--and especially myelofibrosis (MF)--are recognized to be associated with autoimmune phenomena, immune derangements in MPN have been much less studied. Myeloid-derived suppressor cells (MDSC) are one type of important immune modulator cell. Therefore, we studied MDSCs in MPN disease. MDSCs were studied in two cohorts: the first cohort was 55 patients including 16 primary myelofibrosis (PMF), 7 post-polycythemia vera (PV)-MF, 2 post-essential thrombocythemia (ET)-MF, 11 ET, 17 PV, 2 undefined MPN disorder, and 23 normal controls; the second cohort included 38 patients: 17 ET, 7 PMF, 3 ET-MF, 2 PV-MF, 9 PV patients, and 20 normal volunteers. The second cohort was studied using freshly collected specimens and a comparable age group as controls. CD11b(+), CD14(-), and CD33(+) cells were defined as MDSCs in both cohorts by flow cytometry. Since there are no differences in MDSC levels among different MPN categories, they were grouped as MPNs. The results showed that MDSCs were significantly elevated in MPNs compared with controls in both cohorts. We also performed RT-PCR and found that MPN patients have significantly elevated arginase-1 mRNA compared with controls, and sorted MDSCs were found to have suppressor T cell activity in MPNs, substantiating the hypothesis that levels of MDSCs are, in fact, deranged in MPNs. MDSC levels were not correlated with JAK2 status, white blood cells, Hb levels, platelet counts, splenomegaly, or the degree of bone marrow fibrosis (in MF). Further studies in immune therapy involving MDSC inhibitors or differentiation may be developed to treat MPN disease.
尽管人们认识到BCR-ABL阴性骨髓增殖性肿瘤（MPN）——尤其是骨髓纤维化（MF）——与自身免疫现象有关，但MPN中的免疫紊乱却很少被研究。髓系来源的抑制细胞（MDSC）是一类重要的免疫调节细胞。因此，我们对MPN疾病中的MDSC进行了研究。在两个队列中对MDSC进行了研究：第一个队列有55名患者，包括16例原发性骨髓纤维化（PMF）、7例真性红细胞增多症（PV）后骨髓纤维化、2例原发性血小板增多症（ET）后骨髓纤维化、11例ET、17例PV、2例未明确的MPN疾病以及23名正常对照；第二个队列包括38名患者：17例ET、7例PMF、3例ET后骨髓纤维化、2例PV后骨髓纤维化、9例PV患者以及20名正常志愿者。第二个队列使用新鲜采集的标本进行研究，并以年龄相当的组作为对照。在两个队列中，通过流式细胞术将CD11b(+)、CD14(-)和CD33(+)细胞定义为MDSC。由于不同MPN类别之间的MDSC水平没有差异，因此将它们归为MPN组。结果显示，在两个队列中，MPN组的MDSC水平均显著高于对照组。我们还进行了逆转录聚合酶链反应（RT-PCR），发现MPN患者与对照组相比，精氨酸酶-1 mRNA显著升高，并且分选的MDSC在MPN中具有抑制性T细胞活性，证实了MPN中MDSC水平实际上紊乱的假设。MDSC水平与JAK2状态、白细胞、血红蛋白水平、血小板计数、脾肿大或（MF中的）骨髓纤维化程度无关。可能会开展涉及MDSC抑制剂或分化的免疫治疗的进一步研究来治疗MPN疾病。
