Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). Patients with DLBCL harboring MYC aberrations concurrent with BCL2 or/and BCL6 aberrations constitute a specific group with extremely poor outcome. In this study, we retrospectively investigated the incidence and prognosis of MYC, BCL2, and BCL6 aberrations with DLBCL patients in Chinese population. We applied fluorescence in situ hybridization and immunohistochemical analysis in 246 DLBCL patients. The results showed that patients with MYC or BCL2 copy number aberration (CNA) had significantly worse overall survival (OS) and progression-free survival (PFS) than negative cases (P < 0.0001). Patients with both MYC and BCL2 CNA had similar outcomes to those with classic double hit lymphoma or protein double expression lymphoma (MYC and BCL2/BCL6 coexpression). By multivariate analysis, MYC CNA, BCL2 CNA and double CNA were the independent worse prognostic factors. In conclusions, patients with MYC or BCL2 CNA constituted a unique group with extremely poor outcome and may require more aggressive treatment regimens.
Highlights
Diffuse large B-cell lymphoma (DLBCL), which is the most common group of non-Hodgkin lymphomas (NHL), accounts for 30%–40% of all lymphomas
Among the 246 DLBCL patients diagnosed in the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, fluorescence in situ hybridization (FISH) analysis was successfully performed in 240 cases and immunohistochemistry (IHC) analysis in 246 cases
Among 240 cases analyzed by FISH, MYC copy number aberration (CNA) was detected in 18 cases (7.5%), which was less frequent than MYC rearrangement {13.7% [33/240] cases had MYC translocation
Summary
Diffuse large B-cell lymphoma (DLBCL), which is the most common group of non-Hodgkin lymphomas (NHL), accounts for 30%–40% of all lymphomas. The t(14;18) translocation juxtaposes BCL2 to the immunoglobulin heavy chain gene (IGH) enhancer, resulting in BCL2 protein overexpression and inhibition of apoptosis [7]. This translocation is found in 80%–90% of follicular lymphoma and 20%–30% of de novo DLBCL cases [8]. Protein expression (such as MYC and BCL2 or BCL6) had important prognostic value with or without gene aberrations [12,13,14,15,16]. We compared the prognostic differences of double CNA with classic DHL and protein double expression www.impactjournals.com/oncotarget (MYC and BCL2/BCL6 coexpression) lymphoma (DEL) and indicated the special value of double CNA which might be an important supplement to the DHL system
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