RESUMO
Deletions of 11q in chronic lymphocytic leukemia (CLL) are usually associated with progressive disease and poor prognosis. A novel translocation within the previously identified 11q minimal region has been defined in a patient with CLL. The breakpoint is between genes POU2AF1 and BTG4. POU2AF1 is a B-cell-specific transcriptional coactivator, and BTG4 is a member of the BTG family of negative regulators of the cell cycle, making both of them good candidate genes for the pathogenesis of 11q- CLL. POU2AF1 was observed to be differentially expressed in the cells of patients with CLL compared to its expression in normal B cells in the absence of mutations. This may reflect ongoing stimulation and active accessory signaling in CLL cells. BTG4 could contribute to CLL pathogenesis following inactivation by haploinsufficiency.
Assuntos
Proteínas de Ciclo Celular/genética , Cromossomos Humanos Par 11 , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Fatores de Transcrição/genética , Sequência de Bases , Deleção Cromossômica , Mapeamento Cromossômico , Clonagem Molecular , Sequência Consenso , Primers do DNA , DNA de Neoplasias/sangue , DNA de Neoplasias/isolamento & purificação , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Dados de Sequência Molecular , Fator 1 de Transcrição de Octâmero , Reação em Cadeia da Polimerase , RNA Mensageiro/genéticaRESUMO
Adenovirus infections occur in 5% to 21% of patients following stem cell transplantation (SCT), with an associated mortality of up to 50%. However, a lack of prospective studies has hampered further developments in the understanding and management of this infection in the posttransplantation setting. We prospectively studied the incidence and outcome of adenovirus infections after SCT using preemptive screening and a policy of reduction or withdrawal of immunosuppressive therapy if the virus was isolated. The incidence of adenovirus infection was 19.7% (15 of 76), and the virus was isolated exclusively in recipients of T-cell-depleted grafts. Patients receiving 50 or 100 mg alemtuzumab in vivo were at the greatest risk of adenovirus infection (45% probability) regardless of donor type, and this was related to the slower lymphocyte recovery. Six (40%) of the 15 adenovirus-infected patients developed adenovirus disease. Severe lymphocytopenia (less than 300/microL) at the time of first detection of adenovirus was a major risk factor for development of adenovirus disease (P =.001). In addition, failure to reduce immunosuppression (P =.04) and a positive result of adenovirus polymerase chain reaction (PCR) in blood at diagnosis (P =.01) were both associated with fatal adenovirus disease. On the basis of this study, we recommend active surveillance for adenovirus infection in T-cell-depleted SCT and withdrawal or reduction of immunosuppressive treatment, if possible, in patients with adenovirus infection. Preemptive antiviral therapy is warranted for patients with severe lymphocytopenia or positive blood PCR, and in those in whom immunosuppressive therapy cannot be reduced.