Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany.
Blood. 2012 Aug 2;120(5):1087-94. doi: 10.1182/blood-2012-03-415588. Epub 2012 Jun 15.
Annexin A2 (ANXA2) promotes myeloma cell growth, reduces apoptosis in myeloma cell lines, and increases osteoclast formation. ANXA2 has been described in small cohorts of samples as expressed by myeloma cells and cells of the BM microenvironment. To investigate its clinical role, we assessed 1148 samples including independent cohorts of 332 and 701 CD138-purified myeloma cell samples from previously untreated patients together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores, along with expression of ANXA2 in whole BM samples, stromal cells, osteoblasts, osteoclasts, and BM sera. ANXA2 is expressed in all normal and malignant plasma cell samples. Higher ANXA2 expression in myeloma cells is associated with significantly inferior event-free and overall survival independently of conventional prognostic factors and is associated with gene expression-determined high risk and high proliferation. Within the BM, all cell populations, including osteoblasts, osteoclasts, and stromal cells, express ANXA2. ANXA2 expression is increased significantly in myelomatous versus normal BM serum. ANXA2 exemplifies an interesting class of targetable bone-remodeling factors expressed by normal and malignant plasma cells and the BM microenvironment that have a significant impact on survival of myeloma patients.
膜联蛋白 A2（ANXA2）促进骨髓瘤细胞生长，减少骨髓瘤细胞系中的细胞凋亡，并增加破骨细胞的形成。已经在小样本队列中描述了 ANXA2 在骨髓瘤细胞和骨髓微环境细胞中表达。为了研究其临床作用，我们评估了 1148 个样本，包括来自未经治疗的患者的 332 个和 701 个 CD138 纯化的骨髓瘤细胞样本的独立队列，以及临床预后因素、染色体异常和基于基因表达的高危评分，以及整个 BM 样本、基质细胞、成骨细胞、破骨细胞和 BM 血清中的 ANXA2 表达。ANXA2 在所有正常和恶性浆细胞样本中均有表达。骨髓瘤细胞中 ANXA2 的高表达与无事件生存和总生存显著相关，独立于常规预后因素，与基因表达确定的高危和高增殖相关。在 BM 中，包括成骨细胞、破骨细胞和基质细胞在内的所有细胞群均表达 ANXA2。骨髓瘤性 BM 血清中 ANXA2 的表达明显高于正常 BM 血清。ANXA2 是正常和恶性浆细胞以及骨髓微环境中表达的一类有趣的可靶向骨重塑因子的代表，对骨髓瘤患者的生存有重大影响。
