T-Cell Immunoglobulin and Mucin Domain 3 (TIM-3) Gene Expression as a Negative Biomarker of B-Cell Acute Lymphoblastic Leukemia

• Published in: International journal of molecular sciences Vol. 25; no. 20; p. 11148
• Main Authors: Basingab, Fatemah S., Bashanfer, Manar, Alrofaidi, Aisha A., Barefah, Ahmed S., Hammad, Rawan, Alahdal, Hadil M., Alrahimi, Jehan S., Zaher, Kawther A., Hassan, Sabah, Algiraigri, Ali H., El-Daly, Mai M., Alkarim, Saleh A., Aldahlawi, Alia M.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.10.2024; MDPI
• Subjects: Acute lymphocytic leukemia; Adolescent; Biomarkers; Biomarkers, Tumor - genetics; Bone marrow; Cancer therapies; Case-Control Studies; Chemotherapy; Child; Child, Preschool; Cytotoxicity; Development and progression; Female; Gene expression; Gene Expression Regulation, Leukemic; Genetic aspects; Health aspects; Hepatitis A Virus Cellular Receptor 2 - genetics; Hepatitis A Virus Cellular Receptor 2 - metabolism; Humans; Immunity; Immunoglobulins; Immunotherapy; Leukemia; Ligands; Lymphocytes; Male; Medical prognosis; Physiological aspects; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Prognosis; Proteins; Remission (Medicine); Saudi Arabia; acute lymphoblastic leukemia; immune checkpoint receptor (ICR); T-cell immunoglobulin and mucin domain 3; CD4+ T cells; tumor microenvironment; programmed cell death-1; B-cell acute lymphoblastic leukemia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252011148

B-cell acute lymphoblastic leukemia (B-ALL) accounts for 85% of all childhood ALL. Malignancies exhaust T and B cells, resulting in an increased expression of immune checkpoint receptors (ICRs), such as T-cell immunoglobulin and mucin domain 3 (TIM-3). TIM-3 has been found to be dysregulated in different types of cancer. However, there is a lack of rigorous studies on the TIM-3 expression in B-ALL. The current study aimed to measure the expression of TIM-3 at the gene and protein levels and evaluate the potential of TIM-3 as a biomarker in B-ALL. A total of 28 subjects were recruited between 2021 and 2023, comprising 18 subjects diagnosed with B-ALL and 10 non-malignant healthy controls. The B-ALL patients were divided into three groups: newly diagnosed (four patients), in remission (nine patients), and relapse/refractory (five patients). The expression levels of TIM-3 were evaluated using the real-time qPCR and ELISA techniques. The results revealed that the TIM-3 expression was significantly downregulated in the malignant B-ALL patients compared to the non-malignant healthy controls in the mRNA (FC = −1.058 ± 0.3548, p = 0.0061) and protein blood serum (p = 0.0498) levels. A significant TIM-3 gene reduction was observed in the relapse/refractory cases (FC = −1.355 ± 0.4686, p = 0.0327). TIM-3 gene expression allowed for significant differentiation between patients with malignant B-ALL and non-malignant healthy controls, with an area under the curve (AUC) of 0.706. The current study addressed the potential of reduced levels of TIM-3 as a negative biomarker for B-ALL patients.