Cancers (Mar 2021)

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

  • Cheng-Chih Tsai,
  • Yung-Cheng Su,
  • Oluwaseun Adebayo Bamodu,
  • Bo-Jung Chen,
  • Wen-Chiuan Tsai,
  • Wei-Hong Cheng,
  • Chii-Hong Lee,
  • Shu-Min Hsieh,
  • Mei-Ling Liu,
  • Chia-Lang Fang,
  • Huan-Tze Lin,
  • Chi-Long Chen,
  • Chi-Tai Yeh,
  • Wei-Hwa Lee,
  • Ching-Liang Ho,
  • Shiue-Wei Lai,
  • Huey-En Tzeng,
  • Yao-Yu Hsieh,
  • Chia-Lun Chang,
  • Yu-Mei Zheng,
  • Hui-Wen Liu,
  • Yun Yen,
  • Jacqueline Whang-Peng,
  • Tsu-Yi Chao

DOI
https://doi.org/10.3390/cancers13071620
Journal volume & issue
Vol. 13, no. 7
p. 1620

Abstract

Read online

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.

Keywords