氨基酸代谢重塑是癌症的一个标志，导致对氨基酸的营养需求增加。氨基酸对于能量调节、生物合成支持和稳态维持以刺激癌症进展至关重要。然而，苯丙氨酸在多发性骨髓瘤（MM）中的作用仍不清楚。在这里，我们证明 MM 患者血浆中的苯丙氨酸水平降低，但骨髓 (BM) 细胞中的苯丙氨酸水平升高。治疗后，血浆中苯丙氨酸水平升高，BM 中苯丙氨酸水平降低。这表明苯丙氨酸的变化具有诊断价值，并且 BM 微环境中的苯丙氨酸是 MM 进展的重要营养来源。 MM 细胞对苯丙氨酸的需求表现出类似的模式。抑制苯丙氨酸的利用可抑制 MM 细胞生长，并在体外和小鼠模型中与硼替佐米 (BTZ) 治疗产生协同效应。从机制上讲，苯丙氨酸剥夺会诱导过度的内质网应激，并通过 ATF3-CHOP-DR5 途径导致 MM 细胞凋亡。干扰 ATF3 显着影响苯丙氨酸剥夺疗法。总之，我们确定苯丙氨酸代谢是 MM 代谢重塑的一个特征。苯丙氨酸是 MM 增殖所必需的，其异常需求凸显了低苯丙氨酸饮食作为 MM 辅助治疗的重要性。© 2024 作者。

Amino acid metabolic remodeling is a hallmark of cancer, driving an increased nutritional demand for amino acids. Amino acids are pivotal for energetic regulation, biosynthetic support, and homeostatic maintenance to stimulate cancer progression. However, the role of phenylalanine in multiple myeloma (MM) remains unknown. Here, we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow (BM) cells. After the treatment, phenylalanine levels increase in plasma and decrease in BM. This suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM progression. The requirement for phenylalanine by MM cells exhibits a similar pattern. Inhibiting phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib (BTZ) treatment in vitro and murine models. Mechanistically, phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3-CHOP-DR5 pathway. Interference with ATF3 significantly affects phenylalanine deprivation therapy. In conclusion, we have identified phenylalanine metabolism as a characteristic feature of MM metabolic remodeling. Phenylalanine is necessary for MM proliferation, and its aberrant demand highlights the importance of low-phenylalanine diets as an adjuvant treatment for MM.© 2024 The Authors.