Multiple myeloma (MM) is an incurable malignant plasma cell tumor characterized by clonal proliferation of plasma cells in the bone marrow, accompanied by CRAB symptoms such as elevated blood calcium (C), renal damage (R), anemia (A), and bone damage (B). Human leukocyte immunoglobulin like receptor B1 (LILRB1) and CD36 are associated with metabolic abnormalities and immune evasion. Lymphatic enhancer factor 1 (LEF-1) is closely related to tumorigenesis, disease progression, and drug resistance. Optical genome mapping (OGM) technology can comprehensively reflect the cytogenetic changes of patients.

To explore the relationship between changes of LILRB1, CD36 and LEF-1 in the tumor microenvironment and the onset of MM.

76 MM patients who were hospitalized in the Department of Hematology and Oncology, Beijing Chao-yang Hospital, Capital Medical University from December 2023 to January 2025 were selected. They were divided into active MM (aMM group, n=43) and reactive MM (rMM group, n=33) based on their disease status. Meanwhile, 24 healthy individuals who underwent physical examinations at the hospital during the same period and were matched in terms of gender and age were selected as the plasma detection control group (HC group), and 23 patients with benign anemia were selected as the bone marrow plasma detection control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of LILRB1, CD36, and LEF-1 in plasma and bone marrow plasma. Receiver operating characteristic (ROC) curves for plasma and bone marrow plasma LILRB1, CD36, and LEF-1 in diagnosing MM were plotted, and patients were divided into high-expression and low-expression groups based on the cut-off value. Follow-up was conducted for the patients until March 2025, and the progression-free survival (PFS) and overall survival (OS) were recorded. OGM was used to detect cytogenetic abnormalities in 6 MM patients.

In the plasma, the levels of LILRB1 and LEF-1 in the aMM group were higher than those in the HC group and the rMM group (P<0.05); in the bone marrow plasma, the levels of LILRB1 and LEF-1 in the aMM group were higher than those in the benign anemia group and the rMM group (P<0.05). In the plasma, the level of CD36 in the aMM group was higher than that in the HC group and the rMM group (P<0.05). Correlation analysis showed that in plasma, LEF-1 was positively correlated with LILRB1 (r_s=0.403, P=0.007) and CD36 (r_s=0.340, P=0.017), and LILRB1 was positively correlated with CD36 (r_s=0.406, P=0.006). In bone marrow plasma, LEF-1 was positively correlated with LILRB1 (r_s=0.528, P=0.001), and LILRB1 was positively correlated with CD36 (r_s=0.343, P=0.037), whereas no correlation was observed between LEF-1 and CD36 (r_s=0.080, P=0.612). Survival analysis revealed that in plasma, patients with high expression of LILRB1, CD36, and LEF-1 had significantly shorter PFS and OS compared to those with low expression (P<0.05). In bone marrow plasma, patients with high LILRB1 expression had shorter OS, and those with high LEF-1 expression had shorter PFS and OS (P<0.05). OGM testing showed that 3 out of 6 MM patients (50%) had 17q12 (HNF1β) deletion, accompanied by abnormalities such as del (17p), t (4; 14), and high expression of LEF-1. The median PFS and OS were 14 months and 41 months, respectively.

The high expression of LILRB1, CD36 and LEF-1 is associated with disease activity, progression, and poor prognosis in MM. LILRB1 and CD36 may participate in the pathological process of MM through lipid metabolism regulation and immune suppression. OGM testing on 6 MM patients revealed that 50% of them had 17q12 deletion, leading to abnormal expression of HNF1β, an upstream regulatory gene of LEF-1, which activates the Wnt signaling pathway to promote MM development. Therefore, LILRB1, CD36, and LEF-1 are expected to serve as biomarkers and potential therapeutic targets for evaluating MM activity, predicting disease progression, and providing new ideas for MM treatment.