A new digital droplet PCR method for looking at epigenetics in diffuse large B-cell lymphomas: The role of BMI1, EZH2, and USP22 genes

Epigenetics has been shown to be relevant in oncology: BMI1 overexpression has been reported in leukemias, EZH2 mutations have been found in follicular lymphoma, and USP22 seems to stabilize BMI1 protein. In this study, we measured the expression of BMI1, EZH2, and USP22 in lymph nodes from 56 diffu...

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Published in:	International journal of laboratory hematology
Main Authors:	Lusci Gemignani, Alessio, Papotti, Robel, Bomben, Riccardo, Gattei, Valter, Pozzi, Samantha, Donati, Valentina, Bettelli, Stefania, Forti, Elisa, Mansueto, Giovanna, Di Napoli, Arianna, Cox, Maria Christina, Flenghi, Leonardo, Rossi, Pietro, Volpe, Guido, Dardanis, Dimitri, Bono, Clara, Guerrini, Francesca, Morganti, Riccardo, Sacchi, Stefano, Galimberti, Sara
Format:	Journal Article
Language:	English
Published:	England 10-09-2024
Subjects:	ddPCR DLBCL BMI1 USP22 EZH2
Online Access:	Get full text
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Summary:	Epigenetics has been shown to be relevant in oncology: BMI1 overexpression has been reported in leukemias, EZH2 mutations have been found in follicular lymphoma, and USP22 seems to stabilize BMI1 protein. In this study, we measured the expression of BMI1, EZH2, and USP22 in lymph nodes from 56 diffuse large B-cell lymphoma (DLBCL) patients. A new multiplex digital droplet PCR (ddPCR) has been set up to measure the expression of 4 genes (BMI1, EZH2, USP22, and GAPDH) in the same reaction on RNA extracted from paraffin-embedded tissues. The specificity of ddPCR was confirmed by a 100% alignment on the BLAST platform and its repeatability demonstrated by duplicates. A strict correlation between expression of BMI1 and EZH2 and BMI1 and USP22 has been found, and high expression of these genes was correlated with extra-nodal lymphomas. Progression-free survival (PFS) and overall survival (OS) were conditioned by IPI, bone marrow infiltration, and the complete response achievement. High levels of BMI1 and USP22 did not condition the response to therapy, but impaired the PFS, especially for patients defined at "high risk" based on the cell of origin (no germinal center [GCB]), high BCL2 expression, and IPI 3-5. In this subgroup, the probability of relapse/progression was twice higher than that of patients carrying low BMI1 and USP22 levels. High expression of BMI1 and of USP22 might be a poor prognostic factor in DLBCL, and might represent the target for novel inhibitors.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1751-5521 1751-553X 1751-553X
DOI:	10.1111/ijlh.14363