Document Type : Original Article(s)
Authors
1 Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Molecular Pathology and Cytogenetics, Shiraz University of Medical Sciences, Shiraz, Iran
3 Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
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, BCL2, and BCL6 gene rearrangements among Iranian DLBCL patients.
Method: This historical cohort study encompassed 152 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 20 normal controls. Survival data was analyzed using the Kaplan-Meier method and the Log-Rank test.
Results: Among the patients, 7 (4.8%), 4 (2.9%), and 15 (10.2%) exhibited MYC, BCL2, and BCL6 rearrangements, respectively. Additionally, 1.5% of the patients demonstrated double-hit (DH) characteristics with both MYC and BCL2 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 26.6, 31.2, 9.1, and 34.2 months for MYC, BCL2, BCL6-rearranged, and DH tumors, respectively (P > 0.05). 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, BCL2, and/or BCL6 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.
Highlights
Mehdi Montazer (Google Scholar)
Keywords
Main Subjects
How to cite this article:
Radmanesh F, Monabati A, Motavas M, Rezvani A, Montazer M. Prevalence and prognostic impact of MYC, BCL2, and BCL6 rearrangements in large B cell lymphoma patients: a multicenter historical cohort study from Iran. Middle East J Cancer. 2024;15(2):89-97. doi:10.30476/mejc.2023.98321.1891.
- Gascoyne RD, Chen JKC, Campo E, Rosenwald A, Jaffe ES, Stein H, et al. Diffuse large B-cell lymphoma, NOS. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th International Agency for Research on Cancer (IARC): Lyon, France; 2017.p.291-297.
- Naeini YB, Wu A, O'Malley DP. Aggressive B-cell lymphomas: frequency, immunophenotype, and genetics in a reference laboratory population. Ann Diagn Pathol. 2016;25:7-14. doi: 10.1016/j.anndiagpath.2016.07.008.
- Chan ACL, Chan JKC. Diffuse large B-cell lymphoma. In: Jaffe E, Arber DA, Campo E, Harris NL, Quintanilla-Fend L, editors. Hematopathology. 2nd Elsevier: Philadelphia, US; 2017.p.415-444.
- King JF, Lam JT. A practical approach to diagnosis of B-cell lymphomas with diffuse large cell morphology. Arch Pathol Lab Med. 2020;144(2):160-7. doi: 10.5858/arpa.2019-0182-RA.
- Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. 2016;127(20):2375-90. doi: 10.1182/blood-2016-01-643569.
- Eldessouki T, Hanley K, Hamadeh F, Oshilaja OO, Sturgis CD. "Triple hit" lymphomas: A retrospective cytology case series of an uncommon high grade B-cell malignancy with C-MYC, BCL-2 and BCL-6 rearrangements. Diagn Cytopathol. 2018;46(9):807-11. doi: 10.1002/dc.24038.
- Schiefer AI, Kornauth C, Simonitsch-Klupp I, Skrabs C, Masel EK, Streubel B, et al. Impact of single or combined genomic alterations of TP53, MYC, and BCL2 on survival of patients with diffuse large B-cell lymphomas: a retrospective cohort study. Medicine. 2015;94(52): doi: 10.1097/MD.0000000000002388.
- Li W. The 5th Edition of the World Health Organization Classification of Hematolymphoid Tumors. In: Li W, editor. Leukemia [Internet]. Brisbane, Australia: Exon Publications; 2022. [cited 2023 June 5] Available from: https://www.ncbi.nlm.nih.gov/books/NBK586208/
- Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, de Oliveira Araujo IB, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid neoplasms. Leukemia. 2022;36(7):1720-48. doi: 10.1038/s41375-022-01620-2.
- Campo E, Jaffe ES, Cook JR, Quintanilla-Martinez L, Swerdlow SH, Anderson KC, et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. 2022;140(11):1229-53. doi: 10.1182/blood.2022015851.
- Xia Y, Zhang The spectrum of MYC alterations in diffuse large B-cell lymphoma. Acta Haematol. 2020;19:1-9. doi:10.1159/000505892.
- Yan LX, Liu YH, Luo DL, Zhang F, Cheng Y, Luo XL, et al. MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified. PLoS One. 2014;9(8):e104068. doi: 1371/journal.pone.0104068.
- Nosrati A, Monabati A, Sadeghipour A, Radmanesh F, Safaei A, Movahedinia S. MYC, BCL2, and BCL6 rearrangements in primary central nervous system lymphoma of large B cell type. Ann Hematol. 2019;98(1):169-73. doi: 10.1007/s00277-018-3498-z.
- Ting CY, Chang KM, Kuan JW, Sathar J, Chew LP, Wong OLJ, et al. Clinical significance of BCL2, C-MYC, and BCL6 genetic abnormalities, epstein-barr virus infection, CD5 protein expression, germinal center B cell/non-germinal center B-cell subtypes, Co-expression of MYC/BCL2 Proteins and Co-expression of MYC/BCL2/BCL6 proteins in diffuse large B-cell lymphoma: a clinical and pathological correlation study of 120 patients. Int J Med Sci. 2019;16(4):556-66. doi: 10.7150/ijms.27610.
- Cucco F, Barrans S, Sha C, Clipson A, Crouch S, Dobson R, et al. Distinct genetic changes reveal evolutionary history and heterogeneous molecular grade of DLBCL with MYC/BCL2 double-hit. 2020;34(5):1329-41. doi: 10.1038/s41375-019-0691-6.
- Ma Z, Niu J, Cao Y, Pang X, Cui W, Zhang W, et al. Clinical significance of 'double-hit' and 'double-expression' lymphomas. J Clin Pathol. 2020;73(3):126-38. doi: 10.1136/jclinpath-2019-206199.
- Salam DSDA, Thit EE, Teoh SH, Tan SY, Peh SC, Cheah SC. C-MYC, BCL2 and BCL6 translocation in B-cell non-Hodgkin lymphoma cases. J Cancer. 2020;11(1):190-8. doi: 10.7150/jca.36954.
- Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A, et al. Genetic and functional drivers of diffuse large B cell lymphoma. 2017;171(2):481-94.e15. doi: 10.1016/j.cell.2017.09.027.
- Gong J, Zhang Y, Zhang J, Zhang W, Li J, Ru K, et al. Clinical characteristics of high-grade B-cell lymphomas with rearrangement of MYC, bcl-6 and bcl-2. [In Chinese] Zhonghua Bing Li Xue Za Zhi. 2018;47(1):14-8. doi: 10.3760/cma.j.issn.0529-5807.2018.01.004.
)