[5] Burkitt lymphoma is commonly associated with the infection of B cell lymphocytes with the EBV and in these cases is considered to be one form of the Epstein–Barr virus-associated lymphoproliferative diseases.

[10] The mutational landscape in Burkitt lymphoma has recently been found to differ between tumors with and without EBV infection, further strengthening the role of the virus in disease origin.

[15] Ultimately, an increase in aerobic glycolysis plays a role in providing the necessary energy for cellular growth to occur.

[17] Early in the pathogenesis process, DDX3X mutations limit translation (protein synthesis) allowing lymphoma cells to escape MYC induced proteotoxic stress and apoptosis, then later, DDX3Y mutations restore high level protein synthesis (by producing the translational machinery) and leading to increased proliferation of tumor cells.

[17] These sequential DDX3X and DDX3Y mutations are thought to partially explain why Burkitt lymphoma is more common in males as the DDX3Y RNA helicase is only found on the Y chromosome.

[15][3] TCF3 and ID3 mutations lead to continuously active B-cell receptors, explaining the high level of proliferation seen in Burkitt lymphoma.

[3] BCL6 normally helps B cells mature in the germinal center and produce antibodies specific to encountered antigens.

[18][16] Although the specific pathogenic mechanisms of EBV in Burkitt Lymphoma are unclear, there has been an interest in further elucidating these aspects, particularly with the rise of transcriptomics.

[19] Due to their ability to bind complementary mRNA sequences and thereby prevent gene expression, BART miRNAs assist EBV-infected cells in avoiding detection by the immune system.

[19] BART miRNAs may prove to be a new therapeutic target or specific biomarker for Burkitt Lymphoma patients.

However, there needs to be further research into BART miRNAs interact with intrinsic signaling pathways and contribute to malignancy before any further conclusions can be made.

[18] Latently infected B cells can then go on to produce proteins that function to promote cellular growth through modification of normal signaling pathways.

When the DNA of tumor cells is analyzed using electrophoresis, a clonal band can be demonstrated, since identical IgH genes will move to the same position.

On the contrary, when a normal or reactive lymph node is analyzed using the same technique, a smear rather than a distinct band will be seen.

This technique is useful since sometimes benign reactive processes (e.g. infectious mononucleosis) and malignant lymphoma can be difficult to distinguish.

[citation needed] The tumor consists of sheets of a monotonous (i.e., similar in size and morphology) population of medium-sized lymphoid cells with high proliferative and apoptotic activity.

This rapid response to chemotherapy can be hazardous to the patient, as a phenomenon called "tumor lysis syndrome" could occur.

[5] If treatment with an initial chemotherapy regimen of cyclophosphamide, vincristine, prednisolone, and/or other drugs fails to produce meaningful remission or regression, this usually indicates a more severe outcome.

[16] Furthermore, failed initial treatment and return of Burkitt lymphoma after a six-month stint of time serve as a poor prognostic indicator.

[16] Genetic mutations extending beyond the previously described MYC translocation may also serve as negative prognostic indicators.

[16] The endemic variant mainly impacts areas with an increased prevalence of malaria and EBV in Africa and Papua New Guinea.

[16][31] The sporadic variant with an annual incidence 2-3/million is more commonly found in North America and Europe comprising 1-2% of adult lymphomas and 30–40% of NHL cases.

[16][31] There is also an increased risk of developing this variant of Burkitt lymphoma for individuals that have received an organ transplant after 4–5 years.

[34] These TCF3 and ID3 gene mutations in Burkitt correspond to a cell survival pathway that may be found to be amenable to targeted therapy.