Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Haematologica. 2013 Feb;98(2):255-63. doi: 10.3324/haematol.2012.066209. Epub 2012 Aug 28.
Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated B-cell subtypes with different prognoses after rituximab-CHOP. The importance of previously recognized prognostic markers, such as Bcl-2 protein expression and BCL2 gene abnormalities, has been questioned in the new therapeutic era. We analyzed Bcl-2 protein expression, and BCL2 and MYC gene abnormalities by interphase fluorescence in situ hybridization in 327 patients with de novo disease treated with rituximab-CHOP. Isolated BCL2 and MYC rearrangements were not predictive of outcome in our patients as a whole, but only in those with the germinal center subtype of lymphoma. The prognostic relevance of isolated MYC rearrangements was weaker than that of BCL2 isolated translocations, but was probably limited by the rarity of the rearrangements. Seven of eight patients with double hit lymphoma had the germinal center subtype with poor outcome. The germinal center subtype patients with isolated BCL2 translocations had significantly worse outcome than the patients without BCL2 rearrangements (P=0.0002), and their outcome was similar to that of patients with the activated B-cell subtype (P=0.30), but not as bad as the outcome of patients with double hit lymphoma (P<0.0001). Bcl-2 protein overexpression was associated with inferior outcome in patients with germinal center subtype lymphoma, but multivariate analysis showed that this was dependent on BCL2 translocations. The gene expression profiling of patients with BCL2 rearrangements was unique, showing activation of pathways that were silent in the negative counterpart. BCL2 translocated germinal center subtype patients have worse prognosis after rituximab-CHOP, irrespective of MYC status, but the presence of combined gene breaks significantly overcomes the prognostic relevance of isolated lesions.
弥漫性大 B 细胞淋巴瘤可以通过基因表达谱分析分为生发中心和激活 B 细胞亚型，这两种亚型在接受利妥昔单抗-CHOP 治疗后的预后不同。在新的治疗时代，以前被认为具有预后意义的标志物，如 Bcl-2 蛋白表达和 BCL2 基因异常，其重要性受到了质疑。我们分析了 327 例接受利妥昔单抗-CHOP 治疗的初治患者的 Bcl-2 蛋白表达、BCL2 和 MYC 基因异常，并通过间期荧光原位杂交进行检测。在我们的患者中，孤立的 BCL2 和 MYC 重排本身并不能预测预后，但仅在生发中心型淋巴瘤患者中如此。孤立的 MYC 重排的预后相关性弱于 BCL2 孤立易位，但可能受到重排罕见性的限制。8 例双打击淋巴瘤患者中有 7 例为生发中心型，预后不良。具有孤立 BCL2 易位的生发中心型患者的预后明显差于无 BCL2 重排的患者（P=0.0002），其预后与激活 B 细胞型患者相似（P=0.30），但不如双打击淋巴瘤患者的预后差（P<0.0001）。Bcl-2 蛋白过表达与生发中心型淋巴瘤患者的预后不良相关，但多变量分析显示这取决于 BCL2 易位。具有 BCL2 易位的患者的基因表达谱是独特的，显示出在阴性对照中沉默的途径被激活。无论 MYC 状态如何，BCL2 易位的生发中心型患者在接受利妥昔单抗-CHOP 治疗后的预后较差，但联合基因断裂的存在显著克服了孤立病变的预后相关性。
