Abstract
In order to identify reasons for treatment failures when using targeted therapies, we have analyzed the comprehensive molecular profiles of three relapsed, poor-prognosis Burkitt lymphoma cases. All three cases had resembling clinical presentation and histology and all three patients relapsed, but their outcomes differed significantly. The samples of their tumor tissue were analyzed using whole-exome sequencing, gene expression profiling, phosphoproteomic assays, and single-cell phosphoflow cytometry. These results explain different treatment responses of the three histologically identical but molecularly different tumors. Our findings support a personalized approach for patient with high risk, refractory, and rare diseases and may contribute to personalized and customized treatment efforts for patients with limited treatment options like relapsed/refractory Burkitt lymphoma.SummaryThe main aim of this study is to analyze three relapsed Burkitt lymphoma patients using a comprehensive molecular profiling, in order to explain their different outcomes and to propose a biomarker-based targeted treatment. In cases 1 and 3, the tumor tissue and the host were analyzed prospectively and appropriate target for the treatment was successfully implemented; however, in case 2, analyses become available only retrospectively and his empirically based rescue treatment did not hit the right target of his disease.
Highlights
Burkitt lymphoma is a highly aggressive mature B-cell lymphoma commonly associated with translocation of MYC gene
A subset of patients who do not respond to the first-line chemotherapy and who experience relapse have very poor prognosis despite high-dose chemotherapy followed by stem cell transplantation [2]
A 7-year-old previously healthy boy presented with t(8;14) positive abdominal stage III Burkitt lymphoma
Summary
Burkitt lymphoma is a highly aggressive mature B-cell lymphoma commonly associated with translocation of MYC gene. A subset of patients who do not respond to the first-line chemotherapy and who experience relapse have very poor prognosis despite high-dose chemotherapy followed by stem cell transplantation [2]. This subset of patients, for whom further chemotherapy-based therapies are futile, is recently often considered for therapies based on molecular analysis of their tumor tissue. The findings suggest that molecular signatures are unique, and a tissue biomarker-based customized therapy may be the better approach to address these poor prognosis patients than just another biomarker agnostic randomized trial
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