Aukema Sietse M, Kreuz Markus, Kohler Christian W, Rosolowski Maciej, Hasenclever Dirk, Hummel Michael, Küppers Ralf, Lenze Dido, Ott German, Pott Christiane, Richter Julia, Rosenwald Andreas, Szczepanowski Monika, Schwaenen Carsten, Stein Harald, Trautmann Heiko, Wessendorf Swen, Trümper Lorenz, Loeffler Markus, Spang Rainer, Kluin Philip M, Klapper Wolfram, Siebert Reiner
Haematologica. 2014 Apr;99(4):726-35. doi: 10.3324/haematol.2013.091827. Epub 2013 Oct 31.
Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.
影响MYC癌基因的染色体易位是伯基特淋巴瘤的生物学标志，但也出现在其他成熟B细胞淋巴瘤的一个亚组中。如果伴有靶向BCL2和/或BCL6癌基因的染色体断裂，这些MYC易位阳性（MYC(+)）淋巴瘤被称为双打击淋巴瘤，否则称为单打击淋巴瘤。为了表征除伯基特淋巴瘤之外的这些MYC(+)淋巴瘤的生物学特征，在排除基因表达谱定义的分子伯基特淋巴瘤后，我们探讨了80例MYC易位阳性淋巴瘤（31例单打击、46例双打击和3例BCL6状态未知的MYC(+)淋巴瘤）的分子、病理和临床方面。单打击和双打击淋巴瘤的比较显示，在MYC伙伴（免疫球蛋白/非免疫球蛋白）、基因组复杂性、MYC表达或基因表达谱方面没有差异。双打击淋巴瘤更频繁地表现出生发中心B细胞样基因表达谱，并且具有更高的IGH和MYC突变频率。基因表达谱显示BCL6(+)/MYC(+)和BCL2(+)/MYC(+)双打击淋巴瘤之间有130个差异表达基因。BCL2(+)/MYC(+)双打击淋巴瘤更频繁地表现出生发中心B样基因表达谱。根据MYC伙伴（免疫球蛋白/非免疫球蛋白）对所有淋巴瘤进行分析，未发现实质性差异。在这一系列淋巴瘤中，只有少数病例接受了免疫化疗，与分子伯基特淋巴瘤和没有MYC断裂的淋巴瘤的结果相比，单打击和双打击淋巴瘤的预后相似。我们的数据表明，在排除分子伯基特淋巴瘤和儿科病例后，MYC(+)淋巴瘤在生物学上相当同质，单打击和双打击淋巴瘤以及免疫球蛋白-MYC和非免疫球蛋白-MYC(+)淋巴瘤具有各种共同分子特征。
