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Background  Recently, copy number alteration (CNA) of 9p24.1 were demonstrated in 10% of diffuse large b-cell lymphoma (DLBCL), with gene expression and mutation profiles that were similar to those of primary mediastinal large B-cell lymphoma (PMBCL). However, their CNA-based profile and clinical impact still remain unclear.    Methods  Multiplex ligation-dependent probe amplification were employed to investigate the prevalence of  JAK2/PD-L2  amplification in DLBCL and their CNA-based pattern of driver genes. The clinical outcome and characteristics were also analyzed.    Results  Using unsupervised hierarchical clustering, a small group of DLBCL (10.5%, 8/76) was clustered together with PMBCL as Cluster_2, demonstrating amplification of  JAK2  (100%,8/8) and  PD-L2  (75.0%,6/8). This subgroups of DLBCL demonstrated significant higher expression of PD-L1 than those with MYD88 L265P mutation( p  = 0.024). And they exhibited dismal OS and PFS as compared with DLBCL_others( p  = 0.003 and 0.001, respectively), which is similar to DLBCL with MYD88 L265P mutation.    Conclusions  DLBCL with amplification of  JAK2/PD-L2  exhibits CNA pattern that is similar to PMBCL, and demonstrates unfavorable clinical outcome that resembles those with MYD88 L265P mutation. It is essential to identify this subgroup of DLBCL who may acquire more benefits from the JAK2 and PD-L1 signaling inhibition.

DLBCL with amplification of JAK2/PD-L2 exhibits PMBCL-like CNA pattern and worse clinical outcome resembling those with MYD88 L265P mutation