Genetic background of Richter transformation of atypical chronic lymphocytic leukemia to diffuse large B-cell lymphoma - a case study

Atypical chronic lymphocytic leukemia (aCLL) is an indolent lymphoproliferative neoplasm derived from CD19-positive and CD5 or CD23-negative B cells. This paper presents the results of whole genome sequencing (WGS) of lymphoma cells collected from a 29-year-old woman initially diagnosed with aCLL and successfully treated with fludarabine, cyclophosphamide, and rituximab. Eight years later, due to disease progression, she was treated with ibrutinib. After 5 months, her status suddenly deteriorated. PET-CT results suggested Richter transformation (RT). Histopathological examination of nodal lesions confirmed the diagnosis of Diffuse Large B Cell Lymphoma (DLBCL). Finally, the patient was successfully treated with DHAP-R and alloHSCT. WGS of lymphoma cells revealed the presence of pathogenic (COL11A1, MGME1) and likely pathogenic variants (ZMYM3, ALG6, UBA5, and ATG7). Out of these genes, only ZMYM3 is recurrently mutated in B-cell chronic lymphocytic leukemia (B-CLL). The presence of the other lesions requires further studies and indicates the complex molecular background of aCLL transformation to DLBCL. Therefore, the whole-genome variant assessment is worth considering for introduction into a routine procedure at the time of B-CLL diagnosis, especially when RT is suspected.