He Na, Li Guosheng, Liu Jinting, Liu Wancheng, Tian Ruifeng, Ma Daoxin
Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.
Front Immunol. 2024 Nov 20;15:1452035. doi: 10.3389/fimmu.2024.1452035. eCollection 2024.
Chronic myeloid leukemia (CML) is a severe hematological malignancy characterized by BCR-ABL fusion gene. The advent of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL has improved the landscape of CML treatment dramatically. The occurrence of coronavirus disease 2019 (COVID-19) has challenged many cancers. However, its effect on TKI therapy of CML remains unknown.
In this study, we collected peripheral blood from chronic phase CML patients treated with TKIs at low-level BCR-ABL P210 during COVID-19 pandemic, and determined the alterations of BCR-ABL P210 by applying the well-established BCR-ABL P210 detection system.
Our results showed that the level of BCR-ABL P210 of CML patients was significantly elevated shortly after contracting COVID-19, and then recovered to pre-infection level within one month. The elevated degree of P210 was positively correlated with the duration of COVID-19. And the level of P210 was elevated in CML patients that took COVID-19 vaccination. Furthermore, lymphocyte subsets and cytokine detections were performed by flow cytometry to analyze the alteration of immune responses. Our results showed that effector CD8+ T (Teff) cells were significantly downregulated while naïve CD8+ T cells or Treg cells were obviously upregulated in P210-elevated CML patients after contracting COVID-19 compared to that in P210-unchanged or decreased CML patients. Moreover, the SARS-CoV-2 pseudovirus was constructed to further determine its effects. The results showed that the level of BCR-ABL P210 was upregulated upon transfection of SARS-CoV-2 pseudovirus into blood samples of CML patients.
Our results demonstrate that COVID-19 suppresses the immune activity and consequentially elevates the level of BCR-ABL P210 of CML patients.
慢性髓性白血病（CML）是一种以BCR-ABL融合基因为特征的严重血液系统恶性肿瘤。靶向BCR-ABL的酪氨酸激酶抑制剂（TKIs）的出现显著改善了CML的治疗格局。2019年冠状病毒病（COVID-19）的出现给许多癌症带来了挑战。然而，其对CML的TKI治疗的影响尚不清楚。
在本研究中，我们收集了COVID-19大流行期间接受低水平BCR-ABL P210的TKIs治疗的慢性期CML患者的外周血，并应用成熟的BCR-ABL P210检测系统确定BCR-ABL P210的变化。
我们的结果表明，CML患者在感染COVID-19后不久，BCR-ABL P210水平显著升高，然后在一个月内恢复到感染前水平。P210的升高程度与COVID-19的持续时间呈正相关。并且接受COVID-19疫苗接种的CML患者的P210水平升高。此外，通过流式细胞术进行淋巴细胞亚群和细胞因子检测，以分析免疫反应的变化。我们的结果表明，与P210未改变或降低的CML患者相比，感染COVID-19后P210升高的CML患者中效应性CD8+T（Teff）细胞显著下调，而初始CD8+T细胞或调节性T细胞明显上调。此外，构建了SARS-CoV-2假病毒以进一步确定其作用。结果表明，将SARS-CoV-2假病毒转染到CML患者的血液样本中后，BCR-ABL P210水平上调。
我们的结果表明，COVID-19抑制免疫活性，从而升高CML患者的BCR-ABL P210水平。
