Page 130 - Haematologica May 2022

S. Napoli et al.
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Figure 4. GECPAR has a favorable impact on the outcome of germinal center B cell-like diffuse large B-cell lymphoma patients. (A) Kaplan-Meier curves of diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and stratified for GECPAR expres- sion. (B) Kaplan-Meier curves of germinal center B cell-like (GCB)- and activated B cell-like (ABC)-DLBCL patients treated with R-CHOP and stratified for GECPAR expression.
Table S6, left), the other ABC-DLBCL SUDHL2, showed an enrichment of GCB-DLBCL genes (Figure 3E; Online Supplementary Table S6, right), after GECPAR overexpres- sion. Finally, GECPAR transcription was strongly induced by anti-IgM stimulation of the BCR (Online Supplementary Figure S3L). Together, these observations provided further support of GECPAR’s role in maintaining the GC tran- scriptional program.
GECPAR expression has favorable prognostic impact in germinal center diffuse large B-cell lymphoma patients We assessed the expression of GECPAR in 91 DLBCL patients treated with R-CHOP (rituximab, cyclophos- phamide, doxorubicin, vincristine, prednisone) and its potential impact on the clinical outcome. We classified patients in three subgroups: low expressor (below the 15th percentile of the whole population), high expressor (over the 70th percentile), and neutral (in between). High
expressor patients had a higher survival probability than low expressor (P=0.01) (Figure 4A). Then, we looked at the high and low expressors based on their cell of origin. As expected by previous analysis (Online Supplementary Figure S2A), the high expressors were mainly GCB patients. However, among GCB-DLBCL patients, cases with low GECPAR expression had the same risk of death as ABC patients, while the high expressors showed a bet- ter outcome (P=0.03). All together, these observations fur- ther sustain the tumor suppressor role we attributed to GECPAR based on our in vitro experiments.
GECPAR acts in trans regulating cell growth and differentiation by means of Wnt pathway
In order to identify the genes directly regulated by GEC- PAR, we performed CHART-Seq in OCI-LY1 and U2932. We identified 4,172 peaks in OCI-LY1 and 692 peaks in U2932 (Figure 5A; Online Supplementary Tables S7 and S8).
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