Cai Y N, Zhang P H, Fang L H, Liu J Q, Li B, Xu Z F, Qin T J, Xiao Z J
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2020 Dec 14;41(12):1002-1007. doi: 10.3760/cma.j.issn.0253-2727.2020.12.006.
To compare fibrosis-driving cells in patients with primary myelofibrosis (PMF) and patients with myelodysplastic syndromes (MDS) with myelofibrosis (MF) (MDS-MF) . Bone marrow biopsy sections of patients with newly diagnosed PMF and MDS (10 each randomly selected for MF-0/1, MF-2, and MF-3) were stained with specific immunofluorescence antibodies to label Gli1, LeptinR, alpha smooth muscle actin (α-SMA) , CD45, and ProcollagenⅠ. Images captured by confocal microscopy were analyzed by Fiji-ImageJ to calculate the cell counts of Gli1(+), LeptinR(+) cells, and fibrosis-driving cells including α-SMA(+), α-SMA(+)/Gli1(+), α-SMA(+)/LeptinR(+), and ProcollagenⅠ(+)/CD45(+) cells. Patients with PMF and MDS with MF-2/3 had higher LeptinR(+), α-SMA(+), α-SMA(+)/Gli1(+), and Procollagen Ⅰ(+)/CD45(+) cell counts compared with those with MF-0/1 (all values<0.05) . However, patients with PMF with MF-2/3 presented with higher Gli1(+) and α-SMA(+)/LeptinR(+) cell counts than those with MF-0/1 (=0.001 and 0.006) , whereas these cells were similar between patients with MDS with MF-0/1 and MF-2/3 (=0.169 and 0.067) . In patients with MF-0/1, all fibrosis-driving cells did not differ between PMF and MDS (all >0.05) . However, in patients with MF-2/3, Procollagen Ⅰ(+)/CD45(+) cell counts were higher in patients with PMF compared with those with MDS (=0.007) , while other fibrosis-driving cell counts were similar between these two groups (all >0.05) . MF grade and fibrosis-driving cell counts were not correlated with overall survival in patients with either PMF or MDS. α-SMA(+) cells in patients with PMF originated from both Gli1(+) and LeptinR(+) cells, whereas α-SMA(+) cells in patients with MDS-MF only originated from Gli1(+) cells; patients with PMF had higher ProcollagenⅠ(+)/CD45(+) cell counts than those with MDS-MF.
比较原发性骨髓纤维化（PMF）患者与骨髓增生异常综合征（MDS）合并骨髓纤维化（MF）（MDS-MF）患者中驱动纤维化的细胞。对新诊断的PMF和MDS患者的骨髓活检切片（MF-0/1、MF-2和MF-3各随机选取10例）用特异性免疫荧光抗体染色，以标记Gli1、瘦素受体（LeptinR）、α平滑肌肌动蛋白（α-SMA）、CD45和Ⅰ型前胶原。通过共聚焦显微镜捕获的图像用Fiji-ImageJ进行分析，以计算Gli1（+）、LeptinR（+）细胞以及包括α-SMA（+）、α-SMA（+）/Gli1（+）、α-SMA（+）/LeptinR（+）和Ⅰ型前胶原（+）/CD45（+）细胞在内的驱动纤维化细胞的数量。与MF-0/1患者相比，PMF和MF-2/3的MDS患者的LeptinR（+）、α-SMA（+）、α-SMA（+）/Gli1（+）和Ⅰ型前胶原（+）/CD45（+）细胞数量更高（所有P值<0.05）。然而，MF-2/3的PMF患者的Gli1（+）和α-SMA（+）/LeptinR（+）细胞数量高于MF-0/1患者（P=0.001和0.006），而MF-0/1和MF-2/3的MDS患者之间这些细胞相似（P=0.169和0.067）。在MF-0/1患者中，PMF和MDS之间所有驱动纤维化的细胞均无差异（所有P>0.05）。然而，在MF-2/3患者中，PMF患者的Ⅰ型前胶原（+）/CD45（+）细胞数量高于MDS患者（P=0.007），而这两组之间其他驱动纤维化细胞数量相似（所有P>0.05）。MF分级和驱动纤维化细胞数量与PMF或MDS患者的总生存期均无相关性。PMF患者中的α-SMA（+）细胞起源于Gli1（+）和LeptinR（+）细胞，而MDS-MF患者中的α-SMA（+）细胞仅起源于Gli1（+）细胞；PMF患者的Ⅰ型前胶原（+）/CD45（+）细胞数量高于MDS-MF患者。
