Abstract
Introduction Lymphocyte activation gene 3 (LAG3) is an inhibitory checkpoint protein expressed on activated T effector, T regulatory, and natural killer cells. The main function of LAG3 is the regulation of immune homeostasis. Several studies have suggested its role in malignant and autoimmune diseases. The objective of this study was to explore the association between LAG3 single-nucleotide polymorphisms (SNPs) and bone marrow failure diseases. Methods Sixty-two patients newly diagnosed with bone marrow failure diseases in the Hematology Department of Tianjin Medical University General Hospital between January 2019 and December 2020 and 16 healthy controls were enrolled in this study. SNPs in LAG3 were investigated by performing Sanger sequencing, and the association of the detected SNPs with bone marrow failure diseases was analyzed. Results Eleven SNPs were identified. Among them, the frequency of LAG3 rs1941928301 (C>T) was statistically different among the groups (P = 0.013). It was higher in the myelodysplastic syndrome (MDS) group than that in the severe aplastic anemia (SAA) group (P = 0.004) and that in the healthy control group (P = 0.009). Conclusions LAG3 rs1941928301 (C>T) might be associated with a higher risk of MDS. The detected LAG3 SNPs have no apparent effect on susceptibility to SAA and immune-related pancytopenia (IRP).
Highlights
Lymphocyte activation gene 3 (LAG3) is an inhibitory checkpoint protein expressed on activated T effector, T regulatory, and natural killer cells
The bone marrow failure diseases commonly observed are severe aplastic anemia (SAA), mainly caused by the hyperfunction of cytotoxic T lymphocytes; immune-related pancytopenia (IRP), mainly caused by abnormal antibodies produced by B lymphocytes to attack hematopoietic cells; and myelodysplastic syndrome (MDS), a clonal neoplastic disease characterized by the increased risk of transforming into acute myeloid leukemia (AML)
Seven single-nucleotide polymorphisms (SNPs) were identified in patients with MDS, 6 in patients with IRP, and 3 in patients with SAA
Summary
Lymphocyte activation gene 3 (LAG3) is an inhibitory checkpoint protein expressed on activated T effector, T regulatory, and natural killer cells. The bone marrow failure diseases commonly observed are severe aplastic anemia (SAA), mainly caused by the hyperfunction of cytotoxic T lymphocytes; immune-related pancytopenia (IRP), mainly caused by abnormal antibodies produced by B lymphocytes to attack hematopoietic cells; and myelodysplastic syndrome (MDS), a clonal neoplastic disease characterized by the increased risk of transforming into acute myeloid leukemia (AML). As these diseases have different pathogenic mechanisms, the treatment principles of each disease are different. Mechanisms underlying the pathophysiology of these diseases need to be elucidated, and the discovery of specific diagnostic indicators may help in early diagnosis and improvement in patient symptoms and disease prognosis
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