Li Xin, Xu-Monette Zijun Y, Yi Shuhua, Dabaja Bouthaina S, Manyam Ganiraju C, Westin Jason, Fowler Nathan, Miranda Roberto N, Zhang Mingzhi, Ferry Judith A, Medeiros L Jeffrey, Harris Nancy L, Young Ken H
*Department of Oncology, The First Affiliated Hospital Zhengzhou University, Zhengzhou, China Departments of †Hematopathology ‡Radiation Oncology §Bioinformatics and Computational Biology ∥Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center #Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX ¶Department of Pathology, Harvard University Medical School, Boston, MA.
Am J Surg Pathol. 2017 Oct;41(10):1309-1321. doi: 10.1097/PAS.0000000000000923.
Primary bone (PB) diffuse large B-cell lymphoma (DLBCL) is rare and has a favorable prognosis, but the underlying biological mechanisms remain unknown. In this study we analyzed the clinicopathologic features of 160 patients with PB-DLBCL in comparison with 499 nonosseous DLBCL. Compared with patients with nonosseous DLBCL and secondary involvement of bone by DLBCL, PB-DLBCL patients less frequently had elderly age, B-symptoms, elevated serum lactate dehydrogenase levels, and high International Prognostic Index at diagnosis, more frequently had germinal center (GC) subtype (approximately 90%) and complete remission, and had significantly better survival. The 5-year progression-free and overall survival rates of PB-DLBCL patients were 80% and 93%, respectively, superior to both GC B-cell-like (GCB) and activated B cell-like subtypes of DLBCL. Further stratifying nonosseous DLBCL cell-of-origin subtypes by clinical factors showed that PB-DLBCL had similar survival rates as the centrocyte-origin (CC) subtype of DLBCL-GCB classified by the B-cell-associated gene signature algorithm. To better understand the favorable outcome of PB-DLBCL patients, gene expression profiling and microRNA profiling were performed in a small subset of PB-DLBCL. The gene expression profiles of PB-DLBCL resembled those of nonosseous DLBCL-GCB-CC, but were distinct from other DLBCL cell-of-origin especially the centroblast-origin (CB) subtype. Compared with DLBCL-GCB-CB, PB-DLBCL and DLBCL-GCB-CC also had much higher levels of miR-125a-3p, miR-34-3p, and miR-155-5p, and significantly lower levels of miR-17-5p and miR-17-3p. These results demonstrated that PB-DLBCL is clinically distinct, and the cell-of-origin of PB-DLBCL stems from centrocytes in the GC, that are biologically attributed for the favorable prognosis of PB-DLBCL.
原发性骨（PB）弥漫性大B细胞淋巴瘤（DLBCL）较为罕见，预后良好，但其潜在生物学机制尚不清楚。在本研究中，我们分析了160例PB-DLBCL患者的临床病理特征，并与499例非骨DLBCL患者进行了比较。与非骨DLBCL患者及DLBCL继发骨受累患者相比，PB-DLBCL患者在诊断时年龄较大、出现B症状、血清乳酸脱氢酶水平升高及国际预后指数较高的情况较少见，生发中心（GC）亚型（约90%）及完全缓解更为常见，且生存情况明显更好。PB-DLBCL患者的5年无进展生存率和总生存率分别为80%和93%，优于DLBCL的GC B细胞样（GCB）和活化B细胞样亚型。通过临床因素对非骨DLBCL细胞起源亚型进行进一步分层显示，PB-DLBCL的生存率与通过B细胞相关基因特征算法分类的DLBCL-GCB的中心细胞起源（CC）亚型相似。为了更好地理解PB-DLBCL患者良好预后的原因，我们对一小部分PB-DLBCL患者进行了基因表达谱分析和微小RNA谱分析。PB-DLBCL的基因表达谱与非骨DLBCL-GCB-CC相似，但与其他DLBCL细胞起源特别是中心母细胞起源（CB）亚型不同。与DLBCL-GCB-CB相比，PB-DLBCL和DLBCL-GCB-CC中miR-125a-3p、miR-34-3p和miR-155-5p的水平也高得多，而miR-17-5p和miR-17-3p的水平则明显较低。这些结果表明，PB-DLBCL在临床上具有独特性，其细胞起源于GC中的中心细胞，这在生物学上归因于PB-DLBCL的良好预后。
