Bone marrow adipocytes provide early sign for progression from MGUS to multiple myeloma.
Bone marrow adipocytes provide early sign for progression from MGUS to multiple myeloma.
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DOI：
10.18632/oncotarget.28548
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发表时间：
2024-01-16
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影响因子：
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通讯作者：
Jafari, Abbas
中科院分区：
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作者：
El-Masri, Bilal M;Leka, Benedeta;Mustapha, Fatima;Gundesen, Michael Tveden;Hinge, Maja;Lund, Thomas;Andersen, Thomas L;Diaz-delCastillo, Marta;Jafari, Abbas
多发性骨髓瘤（MM）是第二常见的血液恶性肿瘤，其特征是骨髓中恶性浆细胞的克隆性扩增。尽管MM领域最近取得了进展，但该疾病仍然无法治愈。MM之前存在称为意义不明的单克隆丙种球蛋白病（MGUS）的癌前状态，每年进展为MM的风险为1%。建立一种可扩展的方法，改进对进展为MM的高风险MGUS患者的识别，可以改变疾病的临床管理，提高患者的生活质量，并将具有重大的社会经济意义。在这里，我们提供的证据表明，骨髓脂肪组织（BMAT）的变化提供了从MGUS进展到MM的早期迹象。我们采用AI辅助组织学分析未染色的骨髓活检从MGUS受试者或没有进展到MM在10年内（n = 24，n = 17分别）。虽然两组之间的BMAT分数没有差异，但与非进展性MGUS患者相比，发生MM的MGUS患者的骨髓脂肪细胞（BMAd）密度降低。重要的是，两组之间BMAd大小和圆度的分布特征显著不同，表明发生MM的MGUS患者的BMAd大小和圆度增加。BMAT的这些早期变化可以作为从MGUS向MM过渡的有价值的早期指标，可能有助于及时干预和个性化治疗策略。最后，用于未染色骨髓活检组织学表征的基于AI的方法具有成本效益和快速性，使其临床实施可行。
Multiple Myeloma (MM) is the second most common hematological malignancy and is characterized by clonal expansion of malignant plasma cells in the bone marrow. In spite of recent advances in the field of MM, the disease has remained incurable. MM is preceded by a premalignant state known as monoclonal gammopathy of undetermined significance (MGUS), with a risk of progression to MM of 1% per year. Establishing a scalable approach that refines the identification of MGUS patients at high risk of progression to MM can transform the clinical management of the disease, improve the patient’s quality of life, and will have significant socioeconomic implications. Here, we provide evidence that changes in the bone marrow adipose tissue (BMAT) provide an early sign for progression from MGUS to MM. We employed AI-assisted histological analysis of unstained bone marrow biopsies from MGUS subjects with or without progression to MM within 10 years (n = 24, n = 17 respectively). Although the BMAT fraction was not different between the two groups, bone marrow adipocyte (BMAd) density was decreased in MGUS patients who developed MM, compared to non-progressing MGUS patients. Importantly, the distribution profile for BMAd size and roundness was significantly different between the two groups, indicating a shift toward increased BMAd size and roundness in MGUS patients who developed MM. These early changes in the BMAT could serve as valuable early indicators for the transition from MGUS to MM, potentially enabling timely interventions and personalized treatment strategies. Finally, the AI-based approach for histological characterization of unstained bone marrow biopsies is cost-effective and fast, rendering its clinical implementation feasible.