CDKN2A/B 基因突变、PD-1 和 PD-L1 与儿童急性淋巴细胞白血病风险的相关性。
Association of CDKN2A/B mutations, PD-1, and PD-L1 with the risk of acute lymphoblastic leukemia in children.
机构信息
Department of Laboratory Medicine, Hunan Children's Hospital, Changsha, 410007, China.
Pediatrics Research Institute of Hunan Province, Hunan Children's Hospital, Changsha, 410007, China.
出版信息
J Cancer Res Clin Oncol. 2023 Sep;149(12):10841-10850. doi: 10.1007/s00432-023-04974-x. Epub 2023 Jun 14.
PURPOSE
Currently, the significance of CDKN2A/B mutations in the pathogenesis and prognosis of acute lymphoblastic leukemia (ALL) is inconclusive. In this study, we analyzed the genetic and clinical features of children with CDKN2A/B mutations in ALL. In addition, we evaluated the expression and significance of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in serum and explored their role in the susceptibility of childhood ALL.
METHODS
We sequenced CDKN2A/B in the peripheral blood of 120 children with ALL and 100 healthy children with physical examination. The levels of CD4 T, CD8 T, and NK cells were measured by flow cytometry (FCM). Furthermore, the expression of PD-1 and PD-L1 was detected by ELISA.
RESULTS
We found 32 cases of CDKN2A rs3088440 and 11 of CDKN2B rs2069426 in 120 ALL children. Children with ALL in the CDKN2A rs3088440 were more likely to have hepatosplenomegaly (P = 0.019) and high risk (P = 0.014) than the wild group. In contrast, CDKN2B rs2069426 was more likely to develop lymph node metastasis (P = 0.017). The level of PD-L1 in the serum of ALL children was significantly higher than that of the control group, and there was no significant difference in PD-1 (P < 0.001). Additionally, children with CDKN2A rs3088440 had reduced CD8 T cell counts than the wild group (P = 0.039).
CONCLUSION
CDKN2A rs3088440 and CDKN2B rs2069426 may be related to the occurrence and development of ALL in Chinese children. Additionally, PD-1/PD-L1 may be involved in the immune escape process of ALL, which is expected to become a new target for the treatment of the disease.
目的
目前，CDKN2A/B 突变在急性淋巴细胞白血病（ALL）发病机制和预后中的意义尚不清楚。本研究分析了 ALL 中 CDKN2A/B 突变患儿的遗传和临床特征。此外，我们评估了血清中程序性细胞死亡蛋白 1（PD-1）和程序性细胞死亡配体 1（PD-L1）的表达及其在儿童 ALL 易感性中的作用。
方法
我们对 120 例 ALL 患儿和 100 例体检健康儿童的外周血进行了 CDKN2A/B 测序。通过流式细胞术（FCM）测量 CD4 T、CD8 T 和 NK 细胞的水平。此外，通过 ELISA 检测 PD-1 和 PD-L1 的表达。
结果
我们在 120 例 ALL 患儿中发现 32 例 CDKN2A rs3088440 和 11 例 CDKN2B rs2069426。与野生组相比，CDKN2A rs3088440 患儿 ALL 更易发生肝脾肿大（P=0.019）和高危（P=0.014）。相反，CDKN2B rs2069426 更易发生淋巴结转移（P=0.017）。ALL 患儿血清中 PD-L1 水平明显高于对照组，PD-1 无显著差异（P<0.001）。此外，与野生组相比，CDKN2A rs3088440 患儿 CD8 T 细胞计数减少（P=0.039）。
结论
CDKN2A rs3088440 和 CDKN2B rs2069426 可能与中国儿童 ALL 的发生发展有关。此外，PD-1/PD-L1 可能参与 ALL 的免疫逃逸过程，有望成为该病治疗的新靶点。
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