Evaluation of Enzymatic Alterations (ATIC, LDH, ALP) and their relationship with Bone Marrow Infiltration in Multiple Myeloma: AComparative Study Between Newly Diagnosed and Treated Patients

Abstract

Background: The malignant proliferation of monoclonal plasma cells within the bone marrow microenvironment leads to immunodeficiency, bone damage, and metabolic reprogramming. Malignant hematopoietic cells accelerate purine synthesis to meet the nucleotide demands of rapid division; however, the dynamics regarding hematopoietic stem cells remain unclear. Consequently, evaluating enzymatic changes, specifically LDH and ALPin these cells and examining their association with bone marrow infiltration could provide significant clinical insights into disease progression and treatment response in patients with multiple myeloma.

Objective: This study evaluated the clinical utility of serum ATIC levels as a novel biomarker in multiple myeloma and investigated their associations with intramedullary tumor burden, markers of systemic inflammation, conventional enzymes (LDH, ALP), and immunological parameters across treatment stages.

Methodology: In this cross-sectional study, 110 participants were categorized into three groups: newly diagnosed patients (n = 18); patients treated with chemotherapy (n = 47); and an age- and sex-matched healthy control group (n = 50). Serum levels of ATIC, LDH, ALP, β2M, FLC were measured. Also, the percentage of plasma cells in the bone marrow (BMPC%) and the ratios of inflammatory markers—specifically CAR, NLR, and PLR.

Results: A statistically significant increase in serum ATIC levels was observed in newly diagnosed patients (54.32 ± 4.01) compared to the control group (9.12 ± 1.15, P=0.001), with levels decreasing during chemotherapy (25.40 ± 2.12). Linear regression analysis revealed a strong positive correlation between baseline serum ATIC levels and intramedullary tumor burden, significantly outperforming the LDH marker (R²=0.202). This correlation disappeared completely in the group of patients undergoing chemotherapy (R² < 0.10). Dynamic changes in β2M and ALP levels mirrored the trend observed in ATIC levels. Statistically significant elevations in systemic inflammatory markers (CAR, NLR, and PLR) were also noted at diagnosis; these subsequently returned to normal ranges alongside improvements in FLC levels. ROC analysis demonstrated superior diagnostic performance for ATIC (AUC = 0.842; 95% CI: 0.759–0.926; P = 0.001), achieving a sensitivity of 83.3% and a specificity of 26.7% at an optimal cutoff value of 10.23.

Conclusion: Serum ATIC serves as a highly sensitive, non-invasive biomarker for monitoring intramedullary tumor burden and immediate response to chemotherapy in cases of multiple myeloma. Overall, the marked elevation in serum ATIC levels and its strong correlation with the extent of bone marrow plasma cell infiltration demonstrate its diagnostic and monitoring value, supporting the goal of establishing ATIC as a reliable biomarker in clinical oncology.

Bangladesh Journal of Infectious Diseases, June 2026;13(1):386-396