Grzywnowicz Maciej, Karabon Lidia, Karczmarczyk Agnieszka, Zajac Malgorzata, Skorka Katarzyna, Zaleska Joanna, Wlasiuk Paulina, Chocholska Sylwia, Tomczak Waldemar, Bojarska-Junak Agnieszka, Dmoszynska Anna, Frydecka Irena, Giannopoulos Krzysztof
a Department of Experimental Hematooncology , Medical University of Lublin , Lublin , Poland.
b Department of Experimental Therapy , Institute of Immunology and Experimental Therapy, Polish Academy of Science , Wroclaw , Poland.
Leuk Lymphoma. 2015;56(10):2908-13. doi: 10.3109/10428194.2015.1017820. Epub 2015 Mar 14.
Programmed death-1 (PD-1) is a negative receptor expressed on lymphocytes including malignant B cells in chronic lymphocytic leukemia (CLL). In this work, we found that patients with CLL had a higher expression of PD-1 transcript (PDCD1) than healthy volunteers (p < 0.0001). PDCD1 expression was comparable between CLL cells from accumulation (peripheral blood) and proliferation (bone marrow) disease compartments. In blood samples of patients with mutated IGHV genes PDCD1 expression was higher than with unmutated IGHV (p = 0.0299). We demonstrated that phosphorylation of SYK and LYN, key B-cell receptor signaling kinases, was independent of PD-1 expression in patients with CLL, while ZAP-70 phosphorylation in negative tyrosine residue 292 showed strong inverse correlation (r = - 0.8, p = 0.0019). No associations between five single nucleotide polymorphisms of PDCD1, their expressions and susceptibility to CLL were found. In conclusion, PD-1 might be an independent, universal marker of CLL cells and a part of their activated phenotype, and subsequently might modulate the function of ZAP-70.
程序性死亡蛋白1（PD-1）是一种在淋巴细胞（包括慢性淋巴细胞白血病（CLL）中的恶性B细胞）上表达的负性受体。在本研究中，我们发现CLL患者的PD-1转录本（PDCD1）表达高于健康志愿者（p < 0.0001）。来自积聚（外周血）和增殖（骨髓）疾病区室的CLL细胞之间的PDCD1表达相当。在IGHV基因突变患者的血样中，PDCD1表达高于未突变IGHV的患者（p = 0.0299）。我们证明，CLL患者中关键的B细胞受体信号激酶SYK和LYN的磷酸化与PD-1表达无关，而负性酪氨酸残基292处的ZAP-70磷酸化呈强负相关（r = - 0.8，p = 0.0019）。未发现PDCD1的五个单核苷酸多态性与其表达及CLL易感性之间存在关联。总之，PD-1可能是CLL细胞的一个独立、通用的标志物及其活化表型的一部分，随后可能调节ZAP-70的功能。
