RT Journal Article
SR Electronic
T1 Prognostic value of <em>BCL2</em> and <em>TP53</em> genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP
JF Cancer Biology &amp; Medicine
JO Cancer Biology &amp; Medicine
FD China Anti-Cancer Association
SP 893
OP 909
DO 10.20892/j.issn.2095-3941.2021.0193
VO 19
IS 6
A1 Yan Qin
A1 Haizhu Chen
A1 Peng Liu
A1 Changgong Zhang
A1 Jianliang Yang
A1 Lin Gui
A1 Xiaohui He
A1 Liqiang Zhou
A1 Shengyu Zhou
A1 Shiyu Jiang
A1 Hongxin Jiang
A1 Yuankai Shi
YR 2022
UL http://www.cancerbiomed.org/content/19/6/893.abstract
AB Objective: Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2, TP53 and other genetic alterations with outcomes in patients treated with R-CHOP.Methods: Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry.Results: The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications (BCL2GA/AMP) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P &lt; 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes.Conclusions: This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.