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E. Derenzini et al.
the median normalized MYC and BCL-2 mRNA levels, which correlated well with the respective protein levels assessed by IHC (Online Supplementary Figure S2A). MYC/BCL-2 mRNA double expressors (defined as DEXP_mRNA) patients showed a worse outcome com- pared to non-DEXP_mRNA cases (Online Supplementary Figure S2B). Although DEXP_mRNA cases were more prevalent in the ABC compared to the GCB/unclassified (GCB/U) subgroup9 (Online Supplementary Table S3), the
prognostic relevance of the MYC/BCL-2 DEXP_mRNA status was particularly evident in the GCB/U subset (Online Supplementary Figure S2C to F). Focusing the analy- sis on the additional genes (STAT3, NFKBIA, PTEN, PIK3CA), which were selected based on their biologic rel- evance in potentially druggable pathways, only NFKBIA and STAT3 mRNA levels were significantly associated with patient’s outcome, with low STAT3 and low NFKBIA expression predicting worse prognosis (Online
A
Figure 2. Integrating cell of origin with MYC/BCL-2 DEXP_mRNA status for prog- nostication in diffuse large B- cell lymphoma. (A) Recursive partitioning analysis integrat- ing cell of origin (COO) classifi- cation and DEXP_mRNA sta- tus, allowing segregation of patients in three main prog- nostic subgroups (a low risk non-DEXP-mRNA GCB/U sub- set, and two high risk groups: MYC/BCL-2-DEXP-mRNA GCB/U and ABC). (B) Box plot graphs indicating the expres- sion levels of the additional targets included in the panel (MYC, BCL-2, NFKBIA, STAT3, PIK3CA, PTEN) in the three main patients subgroups iden- tified by the recursive parti- tioning analysis (non-DEXP- mRNA GCB/U, MYC/BCL-2 DEXP_mRNA GCB/U, ABC- derived diffuse large B-cell lymphoma [DLBCL]. P-value was calculated with Student t- test by comparing non DEXP_mRNA GCB/U group, selected as a reference, ver- sus other groups. ABC: activat- ed B-cells; GCB: germinal cen- ter B cells; GCB/U: GCB unclassified; DEXP_mRNA: double expressor GCB/U DLBCL. COO Nano: COO as determined by T-GEP with NanoString profiling
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haematologica | 2021; 106(9)