KLK2 single-nucleotide polymorphism rs198977 is associated with increased susceptibility and hyperleukocytosis in AML

Guangqiang Meng; Peng Li; Mingying Li; Yuyan Wu; Yuechan Ma; Tao Sun; Chunyan Ji

doi:10.3389/fgene.2023.1218523

KLK2 single-nucleotide polymorphism rs198977 is associated with increased susceptibility and hyperleukocytosis in AML

Front Genet. 2023 Aug 1:14:1218523. doi: 10.3389/fgene.2023.1218523. eCollection 2023.

Authors

Guangqiang Meng¹, Peng Li¹, Mingying Li¹, Yuyan Wu¹, Yuechan Ma¹, Tao Sun^{1

2}, Chunyan Ji¹

Affiliations

¹ Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
² Shandong Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China.

Abstract

Introduction: Acute myeloid leukemia (AML) is a heterogeneous myeloid malignancy with abnormal molecular diversity. Tissue kallikrein 2 (KLK2) is a kind of serine protease, and has a close relationship with the occurrence and development of malignant tumors. Single nucleotide polymorphism (SNP) of various genes are associated with susceptibility, treatment and survival of AML. Methods: We investigated the association of KLK2 SNPs rs198977 and rs2664155 with AML. We recruited 284 AML patients and 280 healthy controls from the Han population and genotyping KLK2 SNPs rs198977 and rs2664155 by MassARRAY system. Results: Using clinical data from AML patients and controls, including AML susceptibility, blood count, risk stratification, response to induced chemotherapy and survival, our results showed an increased risk of AML susceptibility with KLK2 rs198977 TT genotype in the recessive model. Regarding white blood cell counts in AML patients, the results showed an increased risk of hyperleukocytosis with the TT genotype of KLK2 rs198977 in a codominant model. Moreover, in the recessive model, AML with KLK2 SNPs rs198977 TT genotype had an increased risk of hyperleukocytosis. No significant correlation was found between KLK2 rs2664155 and AML. Discussion: This study suggests that KLK2 rs198977 may be an important genetic factor in the occurrence of AML and hyperleukocytosis in AML, providing a new perspective for disease progression and new therapeutic targets.

Keywords: acute myeloid leukemia; hyperleukocytosis; kallikrein 2; single nucleotide polymorphism; susceptibility.

Grants and funding

This work was supported by grants from the Distinguished Taishan Scholars in Climbing Plan (tspd20210321) and Young Taishan Scholars (tsqn201812132), the National Natural Science Foundation of China (82070160, 81873425, 82170182, and 82270174), the Major Research Plan of the National Natural Science Foundation of China (91942306), the Key Program of Natural Science Foundation of Shandong Province (ZR2020KH016 and ZR2020MH118), the Fundamental Research Funds for the Central Universities (2022JC012), the Independently Cultivate Innovative Teams of Jinan, Shandong Province (2021GXRC050), Multidisciplinary Research and Innovation Team of Young Scholars of Shandong University (2020QNQT007), the Clinical Practical New Technology and Development Fund of Qilu Hospital, Shandong University (2019-5), and China Postdoctoral Science Foundation (2022M711948).