Fatemeh Radmanesh - Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran
Ahmad Monabati - Department of Molecular Pathology and Cytogenetics, Shiraz University of Medical Sciences, Shiraz, Iran
Maedeh Motavas - Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran
Alireza Rezvani - Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Mehdi Montazer - Department of Molecular Pathology and Cytogenetics, Shiraz University of Medical Sciences, Shiraz, Iran

Background: Diffuse large B cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin's lymphoma, characterized by remarkable molecular heterogeneity. This study evaluates the prevalence of MYC, BCL۲, and BCL۶ gene rearrangements among Iranian DLBCL patients.Method: This historical cohort study encompassed ۱۵۲ patients drawn from six reference hospitals who participated in the research. Interphase dual-color break-apart fluorescence in situ hybridization (FISH) was applied to formalin-fixed paraffin-embedded DLBCL specimens categorized as "not otherwise specified" alongside ۲۰ normal controls. Survival data was analyzed using the Kaplan-Meier method and the Log-Rank test.Results: Among the patients, ۷ (۴.۸%), ۴ (۲.۹%), and ۱۵ (۱۰.۲%) exhibited MYC, BCL۲, and BCL۶ rearrangements, respectively. Additionally, ۱.۵% of the patients demonstrated double-hit (DH) characteristics with both MYC and BCL۲ rearrangements, while no triple rearrangements were observed. The presence of rearrangements appeared to be independent of clinicopathological variables. Patients with rearrangements experienced reduced survival durations, with reductions of ۲۶.۶, ۳۱.۲, ۹.۱, and ۳۴.۲ months for MYC, BCL۲, BCL۶-rearranged, and DH tumors, respectively (P > ۰.۰۵). Adverse prognosis was associated with age, activated B-cell-like phenotype, disease stage, B symptoms, lactate dehydrogenase levels, and risk grouping according to the National Comprehensive Cancer Network (NCCN) International Prognostic Index.Conclusion: DLBCL cases featuring MYC, BCL۲, and/or BCL۶ translocations are relatively rare. Patients harboring these rearrangements tend to exhibit aggressive disease progression with shortened overall survival. However, these differences did not reach statistical significance, necessitating further research to validate the incorporation of such tests into the routine workup of DLBCL patients.

diffuse large B cell lymphoma, gene rearrangement, MYC, BCL۲, BCL۶