Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mod Pathol. 2017 Dec;30(12):1688-1697. doi: 10.1038/modpathol.2017.93. Epub 2017 Aug 4.
Patients with double-hit or triple-hit lymphoma have a significantly worse prognosis compared to patients with diffuse large B-cell lymphoma without MYC rearrangement. However, the prognostic importance of extra copies of MYC, BCL2, or BCL6 has not been fully explored. We studied 663 patients with de novo diffuse large B-cell lymphoma in whom the status of MYC/8q24, BCL2/18q21, and BCL6/3q27 were assessed by fluorescence in situ hybridization. Cases of double or triple extra copy lymphoma were defined by the presence of increased MYC copies and increased BCL2 and/or BCL6 copies or rearrangement. In total, 76 patients with diffuse large B-cell lymphoma had MYC extra copies including 43 cases of double or triple extra copy lymphoma; 105 patients had diffuse large B-cell lymphoma with MYC-R including 56 double- or triple-hit lymphoma; and 482 diffuse large B-cell lymphoma patients had no MYC abnormality (MYC normal). Patients with MYC extra copies, similar to MYC-R, had a worse overall survival compared with MYC normal patients (both P<0.01). The prognosis between patients with MYC extra copies and MYC-R was not statistically significantly different (P=0.086). Cell-of-origin classification failed to correlate with survival in the MYC extra copies group, similar to the MYC-R patient group. Compared with patients with double- or triple-hit lymphoma, patients with double or triple extra copy lymphoma had a higher complete remission rate (P=0.02), but there was no significant statistical difference in overall survival (P=0.089). Intensive induction chemotherapy regimens improved the overall survival of patients with double or triple extra copy lymphoma, but there was no significant improvement of overall survival in patients with MYC-R tumors. Multivariate analysis showed that MYC extra copy in diffuse large B-cell lymphoma is an independent poor prognostic factor, similar to MYC rearrangement.
与无 MYC 重排的弥漫性大 B 细胞淋巴瘤患者相比，双打击或三打击淋巴瘤患者的预后明显更差。然而，额外的 MYC、BCL2 或 BCL6 拷贝数的预后意义尚未得到充分探讨。我们研究了 663 例初诊弥漫性大 B 细胞淋巴瘤患者，通过荧光原位杂交评估了 MYC/8q24、BCL2/18q21 和 BCL6/3q27 的状态。双或三额外拷贝淋巴瘤的病例定义为存在增加的 MYC 拷贝数以及增加的 BCL2 和/或 BCL6 拷贝数或重排。共有 76 例弥漫性大 B 细胞淋巴瘤患者存在 MYC 额外拷贝数，其中 43 例为双或三额外拷贝淋巴瘤；105 例弥漫性大 B 细胞淋巴瘤患者存在 MYC-R，其中 56 例为双或三打击淋巴瘤；482 例弥漫性大 B 细胞淋巴瘤患者无 MYC 异常（MYC 正常）。与 MYC 正常患者相比，存在 MYC 额外拷贝数的患者与存在 MYC-R 的患者一样，总体生存率较差（均 P<0.01）。存在 MYC 额外拷贝数的患者与存在 MYC-R 的患者之间的预后无统计学显著差异（P=0.086）。与 MYC-R 患者组相似，在 MYC 额外拷贝组中，细胞起源分类与生存无关。与双或三打击淋巴瘤患者相比，存在双或三额外拷贝淋巴瘤的患者完全缓解率更高（P=0.02），但总体生存率无显著统计学差异（P=0.089）。强化诱导化疗方案改善了双或三额外拷贝淋巴瘤患者的总体生存率，但对 MYC-R 肿瘤患者的总体生存率无显著改善。多变量分析显示，弥漫性大 B 细胞淋巴瘤中的 MYC 额外拷贝是一个独立的预后不良因素，与 MYC 重排相似。
