Molecular subtyping of CD5+ diffuse large B-cell lymphoma based on DNA-targeted sequencing and Lymph2Cx

Abstract

BackgroundCD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) showed poor prognosis in the rituximab era, with limited research on its genetic characteristics and cell of origin (COO). We aimed to demonstrate the molecular characteristics of CD5+ DLBCL and to discover potential prognostic factors.MethodsWe included 24 cases of CD5+ DLBCL and 23 CD5-negative (CD5-) counterparts and collected their clinicopathological features. Targeted DNA sequencing of 475 lymphoma-related genes was performed, and all cases were assigned to distinct genetic subtypes using the LymphGen tool. The COO was determined by the Lymph2Cx assay. The Kaplan–Meier method and Cox proportional hazards model were applied to identify the possible prognostic factors.ResultsCompared with their CD5- counterparts, patients with CD5+ DLBCL tended to have a worse prognosis and a higher incidence of MYD88L265P and CD79B double mutation (MCD) subtype (54.17%, P = 0.005) and activated B cell-like (ABC) subtype (62.5%, P = 00017), as determined by next-generation sequencing and Lymph2Cx, respectively. Moreover, PIM1, MYD88, and KMT2D mutations were detected more frequently in CD5+ DLBCL cases (P < 0.05). According to multivariate analysis, MYC/BCL2 double expression and ABC subtype were correlated with unfavorable overall survival (OS). High mRNA expression of SERPINA9 and MME showed a significant correlation with a better OS, and high expression of MME showed a significant correlation with better progression-free survival in CD5+ DLBCL.ConclusionThe genetic profile of CD5+ DLBCL is characterized by PIM1, MYD88, and KMT2D mutations, with a higher incidence of MCD and ABC subtypes. MYC/BCL2 double expression, ABC subtype, and mRNA expression of SERPINA9 and MME are independently predictive of the prognosis of CD5+ DLBCL.

Toripalimab plus lenalidomide for central nervous system recurrence in refractory CD5+ diffuse large B-cell lymphoma with MYD88 and CD79B comutation: a case report

“…DLBCL with MYD88 L265P and CD79B comutations has inferior outcomes with current standard immunochemotherapy ( 8 ). In addition, MYD88 (L265P) ( 36 , 37 ) and CD5 + DLBCL subtype ( 4 , 10 , 13 ) are both inferior prognostic factor in DLBCLs under current R-CHOP regimens. Zanubrutinib monotherapy has shown promising results in treating relapsed and refractory DLBCL ( 16 ).…”

“…The co-occurrence of MYD88 and CD79B mutations is more commonly observed in primary central nervous system (CNS) DLBCL ( 9 ). In addition, patients with CD5 + DLBCL have a higher incidence of carrying both MYD88 L265P and CD79B mutations ( 10 ).…”

“…R-miniCHOP, an attenuated regimen, is recommended for patients over 80 years without cardiac dysfunction ( 12 ). However, standard R-CHOP chemotherapy or stem cell transplantation has not been shown to benefit patients with the CD5 + DLBCL subtype ( 4 , 10 , 13 ). Recently, novel targeted agents such as ibrutinib, bortezomib, and lenalidomide have been added to R-CHOP to improve DLBCL outcomes ( 14 ).…”

Phosphorylated STAT3 as a potential diagnostic and predictive biomarker in ALK- ALCL vs. CD30high PTCL, NOS

“…The DNA sequencing was performed as described ( 20 ). Specifically, probes targeting at 103 genes ( Table S2 ) related with T/NK cell lymphoma were used to capture the target genes for DNA sequencing.…”