BTLA gene expression and myeloid-derived suppressor cells in newly diagnosed acute myeloid leukemia patients

Abstract

Background Acute myeloid leukemia (AML) is a diverse hematologic cancer that is distinguished by abnormal myeloid development. Because of its impact on the course of disease and the effectiveness of treatment, the immunological microenvironment – in particular, the functions of myeloid-derived suppressor cells (MDSCs) and B and T lymphocyte attenuator (BTLA) – has drawn more attention. Aim To investigate the role of BTLA and MDSCs in newly diagnosed AML patients, examining their relationship with treatment outcomes and prognostic markers. Patients and methods This prospective case–control study was conducted at the Hematology Departments of Kafr El-Sheikh University Hospitals. The study included 50 de novo adult AML patients and 50 healthy controls matched for age, sex, and BMI. Patients were classified into three response groups: complete responders (CR), partial responders (PR), and nonresponders (NR), based on blood counts and bone marrow blast percentages. BTLA expression and MDSC levels were measured and analyzed for associations with treatment response and genetic mutations. Results Among AML patients, 42% achieved CR, 16% PR, 24% were NR, and 18% died during treatment. NRs demonstrated significantly higher median BTLA expression (6.13) and MDSC percentage (8.00) compared to complete responders. Receiver operating characteristic analysis revealed excellent predictive capabilities for both markers, with BTLA (area under the curve=0.917, cutoff ≤2.385) and MDSC% (area under the curve=1.000, cutoff ≤3.500). High BTLA expression (>2.385) was associated with an unfavorable MDSC percentage (>3.5) and poor prognosis. Additionally, low BTLA levels correlated significantly with NPM1 mutations ( P =0.020), indicating a better prognosis, while high BTLA levels were linked to FLT3-ITD mutations ( P <0.001), consistent with poorer outcomes. MDSC levels showed similar associations, underscoring their integrated role in AML pathogenesis and prognosis. Conclusion BTLA expression and MDSC levels are significantly associated with treatment response and genetic prognostic factors in AML. These markers demonstrate predictive capabilities and potential utility for stratifying patients and guiding treatment strategies.