RESUMO
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer in the world, and accounts for 25% of all childhood cancers among children under 15 years of age. Longitudinal studies have shown that children with ALL are born with a deregulated immune response that, together with postnatal environmental exposures, favor the onset of the disease. In this context, IL-10, a key cytokine in the regulation of the immune response, presents itself as a paradoxical mediator, initially influencing the development of ALL through the regulation of inflammatory processes and later on the progression of malignancy, with the increase of this molecule in the leukemia microenvironment. According to the literature, this cytokine plays a critical role in the natural history of the disease and plays an important role in two different though complex scenarios. Thus, in this review, we explore the dual role of IL-10 in ALL, and describe its biological characteristics, immunological mechanisms and genetics, as well as its impact on the leukemia microenvironment and its clinical implications.
Assuntos
Interleucina-10 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Carcinogênese , Citocinas , Interleucina-10/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Microambiente TumoralRESUMO
Inflammation is a physiological mechanism of the immune response and has an important role in maintaining the hematopoietic cell niche in the bone marrow. During this process, the participation of molecules produced by innate immunity cells in response to a variety of pathogen-associated molecular patterns and damage-associated molecular patterns is observed. However, chronic inflammation is intrinsically associated with leukemogenesis, as it induces DNA damage in hematopoietic stem cells and contributes to the creation of the preleukemic clone. Several factors influence the malignant transformation within the hematopoietic microenvironment, with inflammasomes having a crucial role in this process, in addition to acting in the regulation of hematopoiesis and its homeostasis. Inflammasomes are intracellular multimeric complexes responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1ß and interleukin-18 and the cell death process via pyroptosis. Therefore, dysregulation of the activation of these complexes may be a factor in triggering several diseases, including leukemias, and this has been the subject of several studies in the area. In this review, we summarized the current knowledge on the relationship between inflammation and leukemogenesis, in particular, the role of inflammasomes in different types of leukemias, and we describe the potential therapeutic targets directed at inflammasomes in the leukemic context.