N‐Acetylornithine Depletion in Bone Marrow Biopsy: A Novel Microenvironment‐Specific Hallmark for Multiple Myeloma Diagnosis

INTRODUCTION: The bone marrow microenvironment plays crucial roles in the pathogenesis of multiple myeloma. Previous studies have shown that there are differences in the metabolomics of bone marrow suspension and plasma, but there is rare research on bone marrow biopsy tissue. This study aims to establish a new metabolomics approach to analyze bone marrow biopsy tissues and explore its diagnostic value. METHODS: We collected bone marrow biopsy tissues from 19 newly-diagnosed multiple myeloma(MM), 29 monoclonal gammaglobulinemia of undetermined significance(MGUS) and 30 lymphoma without bone marrow invasion as the controls. Metabolomics analysis was conducted using high-performance liquid chromatography-mass spectrometry. Diagnostic Biomarkers and associated pathway were analyzed. RESULTS: The metabolic profiles differed between the controls and MGUS or MM. For MGUS versus MM comparison, Phenylalanyl-Valine and N-Acetylornithine were significantly down-regulated in the MM while N-Acetylornithine has the best diagnostic value with the sensitivity and specificity of 87.5% and 71.4%. For the controls vs. MM comparison, N-Acetylornithine and Aspartyl-Arginine differed markedly. Compared with the controls group, N-Acetylornithine was significantly down-regulated in the MM group, and the AUC of N-Acetylornithine for MM was 0.933, with sensitivity and specificity of (90.0% and 93.3%). N-Acetylornithine displayed the same trends as the comparison between MGUS and MM. Furthermore, when comparing MGUS and MM, Arginine biosynthesis was identified as significantly disrupted in which N-Acetylornithine was involved. CONCLUSIONS: We establish a novel method for metabolomic profiling of bone marrow biopsy tissue and provide evidence of metabolic alterations, particularly reduced N-acetylornithine levels, in MGUS and MM patients.