Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia.

The Journal of Pathology
Maria J García-BarchinoJose A Martinez-Climent

Abstract

The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV- tumours, EBV+ DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV+ DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2-/- IL2γc-/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV+ B-cell clones from 95% of C...Continue Reading

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Citations

Mar 8, 2020·Histopathology·Francisca Inmaculada Camacho CastañedaSocorro María Rodríguez Pinilla
Oct 25, 2020·Journal of Cutaneous Pathology·Francisco M IzquierdoEmiliano Honrado
May 14, 2020·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Vasileios Ionas TheofilouNikolaos G Nikitakis
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Aug 26, 2021·Global Medical Genetics·Darja Kanduc

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