Richter's and prolymphocytic transformation of chronic lymphocytic leukemia are associated with high mRNA expression of activation-induced cytidine deaminase and aberrant somatic hypermutation.
Chronic lymphocytic leukemia (CLL) is an indolent B-cell non-Hodgkin's lymphoma that may transform into higher-grade lymphoma. The transformation involves an increased number of prolymphocytic cells, termed prolymphocytic transformation (PLT) or the development of diffuse large B-cell lymphoma (DLBL), also referred to as Richter's transformation (RT). To analyze whether activation-induced cytidine deaminase (AID), which is essential for somatic hypermutation (SHM) of normal B-cells, and malfunction of SHM termed aberrant somatic hypermutation (ASHM) are associated with higher-grade transformation of CLL, AID mRNA expression and the mutation pattern of c-MYC, PAX-5 and RhoH genes were analyzed in eight cases of CLL without transformation and in 21 cases that showed RT or PLT. Chronic lymphocytic leukemia cases, which showed no transformation or eventually transformed into higher-grade lymphoma, showed low levels of AID mRNA expression and low frequency of mutations of c-MYC, PAX-5 and RhoH genes. In both RT and PLT, high-levels of AID mRNA expression and high-frequency mutations of c-MYC, PAX-5 and RhoH genes were detected. These results indicate that AID expression and ASHM are associated with higher-grade transformation of CLL and provide further evidences that AID expression and ASHM may be activated during the clonal history of B-cell lymphomas.
1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
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Reiniger
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Bödör
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Bognár
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Balogh
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Csomor
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Szepesi
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Kopper
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Matolcsy
D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D003564:Cytidine Deaminase / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D051757:PAX5 Transcription Factor / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C447841:RhoH protein, human; D014157:Transcription Factors; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; D020741:rho GTP-Binding Proteins