RESUMO
The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is uniquely characterized by the presence of stereotyped B-cell receptors (BCRs). A major BCR stereotype in CLL is shared by immunoglobulin G-switched cases utilizing the immunoglobulin heavy-chain variable 4-34 (IGHV4-34) gene. Increased titers of IGHV4-34 antibodies are detected in selective clinical conditions, including infection by B-cell lymphotropic viruses, particularly Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In this context, we sought evidence for persistent activation by EBV and CMV in CLL cases expressing the IGHV4-34 gene. The study group included 93 CLL cases with an intentional bias for the IGHV4-34 gene. On the basis of real-time PCR results for CMV/EBV DNA, cases were assigned to three groups: (1) double-negative (59/93); (2) single-positive (CMV- or EBV-positive; 25/93); (3) double-positive (9/93). The double-negative group was characterized by heterogeneous IGHV gene repertoire. In contrast, a bias for the IGHV4-34 gene was observed in the single-positive group (9/25 cases; 36%). Remarkably, all nine double-positive cases utilized the IGHV4-34 gene; seven of nine cases expressed the major BCR stereotype as described above. In conclusion, our findings indicate that the interactions of CLL progenitor cells expressing distinctive IGHV4-34 BCRs with viral antigens/superantigens might facilitate clonal expansion and, eventually, leukemic transformation. The exact type, timing and location of these interactions remain to be determined.
Assuntos
Citomegalovirus/fisiologia , Herpesvirus Humano 4/fisiologia , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/virologia , Receptores de Antígenos de Linfócitos B/genética , Idoso , Linfócitos B/imunologia , Linfócitos B/patologia , Estudos de Casos e Controles , Estudos de Coortes , Progressão da Doença , Feminino , Genoma Viral , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Hipermutação Somática de Imunoglobulina , Fatores de Tempo , Ativação ViralAssuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Doadores de Tecidos , Adulto , Feminino , Proteínas de Fusão bcr-abl/análise , Células-Tronco Hematopoéticas/patologia , Humanos , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Transplante HomólogoRESUMO
Myelodysplastic syndrome (MDS) in patients treated for acute promyelocytic leukemia (APL) is a rare event. We describe a patient with APL who developed MDS 40 months after entering complete remission (CR). Karyotypic analysis revealed monosomy 5 and 7, which are cytogenetic changes usually occurring after the use of alkylating agents. The patient had received only anthracyclines as potential leukemogenic drugs. A review of the literature on t-AML/MDS occurring after successful therapy for APL showed three similar cases. These observations suggest that anthracyclines may cause t-AML/MDS similar to that induced by alkylating agents.