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

Autor: Lusci Gemignani A; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Papotti R; International PhD School in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy., Bomben R; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Gattei V; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Pozzi S; Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy., Donati V; Pathology II, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Bettelli S; Patologia Molecolare e Medicina Predittiva, AOU Modena, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy., Forti E; Patologia Molecolare e Medicina Predittiva, AOU Modena, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy., Mansueto G; IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy., Di Napoli A; Department of Clinical and Molecular Medicine, Sapienza University, Sant'Andrea University Hospital, Rome, Italy., Cox MC; Haematology Department, King's College Hospital NHS Trust and UOC Ematologia, AOU Sant'Andrea, Roma, Italy., Flenghi L; Department of Emergency and Organ Transplantation, Azienda Ospedaliera di Perugia, Italy., Rossi P; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Volpe G; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Dardanis D; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Bono C; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Guerrini F; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Morganti R; SOD supporto statistico agli studi clinici, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy., Sacchi S; Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy., Galimberti S; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Jazyk: angličtina
Zdroj: International journal of laboratory hematology [Int J Lab Hematol] 2024 Sep 10. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1111/ijlh.14363
Abstrakt: Introduction: 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.
Methods: 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.
Results: 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.
Conclusion: High expression of BMI1 and of USP22 might be a poor prognostic factor in DLBCL, and might represent the target for novel inhibitors.
(© 2024 The Author(s). International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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