Alessio Lusci Gemignani, Robel Papotti, Riccardo Bomben, Valter Gattei, Samantha Pozzi, Valentina Donati, Stefania Bettelli, Elisa Forti, Giovanna Mansueto, Arianna Di Napoli, Maria Christina Cox, Leonardo Flenghi, Pietro Rossi, Guido Volpe, Dimitri Dardanis, Clara Bono, Francesca Guerrini, Riccardo Morganti, Stefano Sacchi, Sara Galimberti
{"title":"A new digital droplet PCR method for looking at epigenetics in diffuse large B‐cell lymphomas: The role of BMI1, EZH2, and USP22 genes","authors":"Alessio Lusci Gemignani, Robel Papotti, Riccardo Bomben, Valter Gattei, Samantha Pozzi, Valentina Donati, Stefania Bettelli, Elisa Forti, Giovanna Mansueto, Arianna Di Napoli, Maria Christina Cox, Leonardo Flenghi, Pietro Rossi, Guido Volpe, Dimitri Dardanis, Clara Bono, Francesca Guerrini, Riccardo Morganti, Stefano Sacchi, Sara Galimberti","doi":"10.1111/ijlh.14363","DOIUrl":null,"url":null,"abstract":"IntroductionEpigenetics has been shown to be relevant in oncology: <jats:italic>BMI1</jats:italic> overexpression has been reported in leukemias, <jats:italic>EZH2</jats:italic> mutations have been found in follicular lymphoma, and <jats:italic>USP22</jats:italic> seems to stabilize BMI1 protein. In this study, we measured the expression of <jats:italic>BMI1, EZH2</jats:italic>, and <jats:italic>USP22</jats:italic> in lymph nodes from 56 diffuse large B‐cell lymphoma (DLBCL) patients.MethodsA new multiplex digital droplet PCR (ddPCR) has been set up to measure the expression of 4 genes (<jats:italic>BMI1, EZH2, USP22</jats:italic>, and <jats:italic>GAPDH</jats:italic>) in the same reaction on RNA extracted from paraffin‐embedded tissues.ResultsThe 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 <jats:italic>BMI1</jats:italic> and <jats:italic>EZH2</jats:italic> and <jats:italic>BMI1</jats:italic> and <jats:italic>USP22</jats:italic> 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 <jats:italic>BMI1</jats:italic> and <jats:italic>USP22</jats:italic> 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 <jats:italic>BMI1</jats:italic> and <jats:italic>USP22</jats:italic> levels.ConclusionHigh expression of <jats:italic>BMI1</jats:italic> and of <jats:italic>USP22</jats:italic> might be a poor prognostic factor in DLBCL, and might represent the target for novel inhibitors.","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Laboratory Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ijlh.14363","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
IntroductionEpigenetics 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.MethodsA 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.ResultsThe 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.ConclusionHigh expression of BMI1 and of USP22 might be a poor prognostic factor in DLBCL, and might represent the target for novel inhibitors.
期刊介绍：
The International Journal of Laboratory Hematology provides a forum for the communication of new developments, research topics and the practice of laboratory haematology.
The journal publishes invited reviews, full length original articles, and correspondence.
The International Journal of Laboratory Hematology is the official journal of the International Society for Laboratory Hematology, which addresses the following sub-disciplines: cellular analysis, flow cytometry, haemostasis and thrombosis, molecular diagnostics, haematology informatics, haemoglobinopathies, point of care testing, standards and guidelines.
The journal was launched in 2006 as the successor to Clinical and Laboratory Hematology, which was first published in 1979. An active and positive editorial policy ensures that work of a high scientific standard is reported, in order to bridge the gap between practical and academic aspects of laboratory haematology.
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