Background/Objectives: Despite its heterogeneity and diagnostic challenges, acute myeloid leukemia (AML) originates from stem cell transformation and alterations in the hematopoietic niche (HN) could be related to leukemic transformation. Therefore, the aim of this study was to evaluate the protein profile of HN from AML patients and compare it with the profile of healthy donors (HDs). Methods: A proteomic analysis was conducted to identify differentially expressed (DE) proteins in BM plasma from AML patients and HD. In silico analysis was performed to identify biological processes and signaling pathways involved. Additionally, ELISA confirmed the expression of the DE protein of interest in BM plasma samples. Results: Proteomic analysis revealed alterations in the plasma profiles of AML patients and 36 DE proteins were found. Among then, we highlight C8G, CFB, SAA1, SERPINA3 and SERPINC1, which are related to inflammatory response process. Thus, considering the role of the secreted protein SAA1 in the inflammatory context and that it is described as a potential biomarker in several tumors, we selected SAA1 for ELISA confirmation. The results corroborated our findings, indicating that increased expression of SAA1 could be related to AML. Our results also revealed that SAA1 can stimulate immune signaling through NF-kappa-B activation. Conclusions: These findings position SAA1 as a promising biomarker for AML diagnosis, offering a potential tool for more accurate identification of the disease. Nevertheless, further studies are needed to understand the relationship of SAA1 with the leukemic transformation process in AML and its potential clinical use.