RESUMO
Leishmaniasis is a disease of the immunocompetent population, more often affecting infants and young children. However, the number of leishmaniasis cases associated with immunosuppression has increased over the last 20 years. The visceral form of the disease, visceral leishmaniasis (VL), is identified as an opportunistic infection in immunosuppressed individuals, occurring mainly after solid organ transplantation, especially in renal transplant recipients. Limited data are available about VL after hematopoietic stem cell transplantation (HSCT). We report the cases of 3 patients with late VL after allogeneic HSCT, and review the literature.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leishmaniose/etiologia , Adulto , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B-cell receptors and also exhibiting distinct prognoses. Here, we analyzed the mutation status of NOTCH1, SF3B1 and BIRC3 in three subsets with particularly poor prognosis, that is, subset #1, #2 and #8, aiming to explore links between genetic aberrations and immune signaling. A remarkably higher frequency of SF3B1 mutations was revealed in subset #2 (44%) versus subset #1 and #8 (4.6% and 0%, respectively; P<0.001). In contrast, the frequency of NOTCH1 mutations in subset #2 was only 8%, lower than the frequency observed in either subset #1 or #8 (19% and 14%, respectively; P=0.04 for subset #1 versus #2). No associations were found for BIRC3 mutations that overall were rare. The apparent non-random association of certain mutations with stereotyped CLL subsets alludes to subset-biased acquisition of genomic aberrations, perhaps consistent with particular antigen/antibody interactions. These novel findings assist in unraveling specific mechanisms underlying clinical aggressiveness in poor-prognostic stereotyped subsets, with far-reaching implications for understanding their clonal evolution and implementing biologically oriented therapy.