Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

Hussam Zawam; Noha E.  Ibrahim; Rasha Salama; Mai Samir; Walaa Abdelfattah; Doaa M. El Demerdash; Dina Sabry; Sahar A. Tabak; Rasha A. Khairy

doi:10.3889/oamjms.2021.5697

Authors

Hussam Zawam Kasralainy Center of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
Noha E. Ibrahim Department of Microbial Biotechnology, Genetic Engineering and Biotechnology Division, National Research Centre, Giza, Egypt
Rasha Salama Kasralainy Center of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
Mai Samir Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt
Walaa Abdelfattah Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo Egypt
Doaa M. El Demerdash Department of Internal Medicine, Clinical Hematology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
Dina Sabry Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt
Sahar A. Tabak Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
Rasha A. Khairy Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt

DOI:

https://doi.org/10.3889/oamjms.2021.5697

Keywords:

DLBCL, MYD88, EZH2, BCL211, Gene polymorphism, Cell of origin

Abstract

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes.

METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients.

RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age <50 years (p <0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p <0.0001), good IPI score (p=0.009), absence of extranodal disease (p <0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype.

CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy.

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