Expression of immune checkpoint molecules in Iraqi acute myeloid leukemia patients

BACKGROUND: Acute myeloid leukemia (AML) is a malignant disease of the bone marrow in which hematopoietic precursors are arrested in an early stage of development leading to production of abnormal cells. AML is the most common type of leukemia in adults. The most important advances can be achieved through immune checkpoint (IC) inhibitors, including cytotoxic T lymphocyte antigen 4 (CTLA-4), Programmed Death protein-1 (PD-1), and anti-programmed ligand 1 in cancer treatment over the past decade. OBJECTIVES: The aims of the current study were to evaluate the expression of CD3, CD28, CD152, CD223, and CD279 markers in T cells by flow cytometry and the expression of PD 1, CTLA 4, and lymphocyte activation gene 3 (LAG 3) expression by real time PCR in AML patients. MATERIALS AND METHODS: This is case control study carried out on 50 AML Iraqi patients, in addition to 50 apparently health person. This study was conducted at the National Center for Hematology, Department of Biology, Mustansiriyah University, and in Baghdad teaching hospital in Medical City, from January 2019 to June 2020. Moreover, the study aims to evaluate the expression of CD3, CD28, CD152, CD223, and CD279 markers in T cells by flow cytometry of AML patients and the expression of PD 1, CTLA 4, and lymphocyte activation gene 3 (LAG 3) expression by real time PCR in AML patients. RESULTS: The cellular expression of almost CD markers did not show a relationship between gender and age. Most AML patients had high CD3 and CD28 expression in cellular expression of T cells. Although there were increasing gene expression of PD-1 and LAG-3 in T cells. The cellular expression of CD279 PD-1 was high, gene expression of CTLA-4 had slightly increased, and cellular expression of CD152 CTLA-4 not significant among healthy controls. In the present manuscript, there was an increase in the expression of PD-1 CD279 in the relapse and refectory patients than the complete and partial remission, while CD3, CD28, and CD223 LAG-3 did not show differences in the expression on T cells among AML stages. Finally, the immunophenotyping of 48 from 50 patients (96%) of the present study was CD3+CD28+CD152-CD279+CD223-. CONCLUSION: Elevate the expression of PD 1, LAG 3 in almost all AML patients associated with the progression of the disease. 96% of AML patients' immunophenotyping was CD3+CD28+CD152-CD279+CD223-.