High-Grade B-Cell Lymphoma (HGBL) with MYC and BCL2 and/or BCL6 Rearrangements Is Predominantly BCL6-Rearranged and BCL6-Expressing in Taiwan

Abstract

This study investigated the epidemiological and clinical peculiarities of BCL2 and BCL6 rearrangement in patients with high grade B-cell lymphoma (HGBL) from Taiwan, compared with data from Western countries. Two hundred and eighty-two DLBCL cases from Taipei Medical University-affiliated hospitals (n = 179) and Tri-Service General Hospital (n = 103) were enrolled for this study. From the 282, 47 (16.7%) had MYC translocation; 24 of these harbored concurrent BCL2 and/or BCL6 translocation (double-hit, DH or triple-hit, TH). Twelve DH-HGBL cases had simultaneous MYC and BCL6 translocations, 8 harbored MYC and BCL2 rearrangement, while the remaining 4 patients exhibited TH. Together, 66.7% of DH/TH-HGBL patients were BCL6 rearrangement positive. Among these BCL6-rearranged DH/TH-HGBL patients, only 6 (37.5%) overexpressed MYC and BCL6 proteins simultaneously, indicating that MYC-BCL6 co-overexpression may not be plausible surrogate biomarker for screening BCL6-rearranged DH-HGBL. By the end of year 5, all patients with TH-HGBL, BCL2 DH-HGBL and all but one BCL6 DH-HGBL cases had expired or were lost to follow-up. Progression-free survival (PFS) was longer for the non-DH/TH-HGBL group compared with the DH/TH-HGBL group. While the patients with BCL2 DH-HGBL were lost to follow-up by day 800, their remaining TH-HGBL and BCL6 DH-HGBL peers exhibited very poor PFS, regardless of age strata. More so, patients with BCL6 rearrangement were 5.5-fold more likely associated with extranodal involvement compared with their BCL2-rearranged peers. Moreover,~60.0% of the BCL6-rearranged DH-HGBL cases were non-GCB, suggesting that including screening for BCL6 rearrangement in patients with the non-GCB phenotype may aid medical decision-making and therapeutic strategy. Contrary to contemporary data from western countries, 2 in every 3 patients with DH/TH-HGBL in Taiwan harbor BCL6 rearrangement. Consistent with present findings, we recommend mandatory screening for BCL6 rearrangement in patients with aggressive HGBL in Taiwan.

Machine Learning Models for the Diagnosis and Prognosis Prediction of High-Grade B-Cell Lymphoma

“…Interestingly, we found that MYC/Bcl-2 HGBL-DH constitutes the majority of HGBL-DH in most European and American studies ( 16 , 26 – 29 ), such as in the United States, France, and Canada. In contrast, some studies from China’s southern regions like the Guangdong and Taiwan Provinces ( 30 , 31 ) showed that MYC/Bcl-6 HGBL-DH is the most common. We consider that it may be due to geographical differences or the relatively small number of specimens.…”

Copy Number Alteration and Mutational Profile of High-Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements, Diffuse Large B-Cell Lymphoma with MYC-Rearrangement, and Diffuse Large B-Cell Lymphoma with MYC-Cluster Amplification

“…has recently analyzed 282 cases of DLBCL and identified 47 (16.7%) with MYC translocation, which included 24 DH/THL [ 53 ]. A total of 62.5% of the DH/THL were GCB, and DH/THL cases were associated with an unfavorable overall survival [ 53 ]. This research is similar to our project.…”

“…We did not compare with DLBCL, which was not otherwise specified. Nevertheless, we have recently shown that cases with high gene expression of BCL2 , MYC , and ENO3 are associated with an unfavorable overall survival of the patients [ 47 , 55 , 56 ], and that HGBL accounts for around 10% of the cases [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ] and is characterized by higher CD163 but lower PTX3 expression [ 57 ]. Therefore, this WHO subtype is being characterized progressively.…”

Lack of reproducibility of histopathological features in MYC‐rearranged large B cell lymphoma using digital whole slide images: a study from the Lunenburg lymphoma biomarker consortium

“…Diagnostic criteria are carefully formulated in the revised 4th and 5th editions of the World Health Organisation (WHO) classification, as well as the International Consensus Classification (ICC), based on investigations in the field. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] LBCL are designated as high-grade B cell lymphoma (HGBL) based on morphological criteria. If a MYC rearrangement (MYC-R) is accompanied by BCL2 and/or BCL6, a diagnosis of HGBL with MYC and BCL2/BCL6 [also known as double-hit (DH) or triple-hit (TH) lymphoma] is made.…”