Khan Maliha, Carmona Selena, Sukhumalchandra Pariya, Roszik Jason, Philips Anne, Perakis Alexander A, Kerros Celine, Zhang Mao, Qiao Na, John Lisa S St, Zope Madhushree, Goldberg Jonathan, Qazilbash Mariam, Jakher Haroon, Clise-Dwyer Karen, Qiu Yihua, Mittendorf Elizabeth A, Molldrem Jeffrey J, Kornblau Steven M, Alatrash Gheath
Department of Leukemia, MD Anderson Cancer Center, Houston, TX, United States.
Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, United States.
Front Immunol. 2018 Jan 25;8:1975. doi: 10.3389/fimmu.2017.01975. eCollection 2017.
Cathepsin G (CG) is a myeloid azurophil granule protease that is highly expressed by acute myeloid leukemia (AML) blasts and leukemia stem cells. We previously identified CG1 (FLLPTGAEA), a human leukocyte antigen-A2-restricted nonameric peptide derived from CG, as an immunogenic target in AML. In this report, we aimed to assess the level of CG expression in acute lymphoid leukemia (ALL) and its potential as an immunotherapeutic target in ALL. Using RT-PCR and western blots, we identified CG mRNA and protein, respectively, in B-ALL patient samples and cell lines. We also examined CG expression in a large cohort of 130 patients with ALL reverse-phase protein array (RPPA). Our data show that CG is widely expressed by ALL and is a poor prognosticator. In addition to endogenous expression, we also provide evidence that CG can be taken up by ALL cells. Finally, we demonstrate that patient ALL can be lysed by CG1-specific cytotoxic T lymphocytes . Together, these data show high expression of CG by ALL and implicate CG as a target for immunotherapy in ALL.
组织蛋白酶G（CG）是一种髓系嗜天青颗粒蛋白酶，在急性髓系白血病（AML）原始细胞和白血病干细胞中高表达。我们之前鉴定出CG1（FLLPTGAEA），一种源自CG的人白细胞抗原A2限制性九聚体肽，作为AML中的免疫原性靶点。在本报告中，我们旨在评估急性淋巴细胞白血病（ALL）中CG的表达水平及其作为ALL免疫治疗靶点的潜力。使用逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法，我们分别在B-ALL患者样本和细胞系中鉴定出了CG信使核糖核酸（mRNA）和蛋白质。我们还通过130例ALL患者的大样本队列逆转相蛋白质芯片（RPPA）检测了CG的表达。我们的数据表明，CG在ALL中广泛表达，且是一个不良预后指标。除了内源性表达，我们还提供证据表明ALL细胞可以摄取CG。最后，我们证明CG1特异性细胞毒性T淋巴细胞可以裂解患者的ALL细胞。总之，这些数据表明ALL中CG高表达，并提示CG作为ALL免疫治疗的靶点。
