Both SEPT2 and MLL are down-regulated in MLL-SEPT2 therapy-related myeloid neoplasia

<p>Abstract</p> <p>Background</p> <p>A relevant role of septins in leukemogenesis has been uncovered by their involvement as fusion partners in <it>MLL</it>-related leukemia. Recently, we have established the <it>MLL-SEPT2 </it>gene fusion as the molecular abnormality subjacent to the translocation t(2;11)(q37;q23) in therapy-related acute myeloid leukemia. In this work we quantified <it>MLL </it>and <it>SEPT2 </it>gene expression in 58 acute myeloid leukemia patients selected to represent the major AML genetic subgroups, as well as in all three cases of <it>MLL-SEPT2</it>-associated myeloid neoplasms so far described in the literature.</p> <p>Methods</p> <p>Cytogenetics, fluorescence in situ hybridization (FISH) and molecular studies (RT-PCR, qRT-PCR and qMSP) were used to characterize 58 acute myeloid leukemia patients (AML) at diagnosis selected to represent the major AML genetic subgroups: <it>CBFB-MYH11 </it>(n = 13), <it>PML-RARA </it>(n = 12); <it>RUNX1-RUNX1T1 </it>(n = 12), normal karyotype (n = 11), and <it>MLL </it>gene fusions other than <it>MLL-SEPT2 </it>(n = 10). We also studied all three <it>MLL-SEPT2 </it>myeloid neoplasia cases reported in the literature, namely two AML patients and a t-MDS patient.</p> <p>Results</p> <p>When compared with normal controls, we found a 12.8-fold reduction of wild-type <it>SEPT2 </it>and <it>MLL-SEPT2 </it>combined expression in cases with the <it>MLL-SEPT2 </it>gene fusion (p = 0.007), which is accompanied by a 12.4-fold down-regulation of wild-type <it>MLL </it>and <it>MLL-SEPT2 </it>combined expression (p = 0.028). The down-regulation of <it>SEPT2 </it>in <it>MLL-SEPT2 </it>myeloid neoplasias was statistically significant when compared with all other leukemia genetic subgroups (including those with other <it>MLL </it>gene fusions). In addition, <it>MLL </it>expression was also down-regulated in the group of <it>MLL </it>fusions other than <it>MLL-SEPT2</it>, when compared with the normal control group (p = 0.023)</p> <p>Conclusion</p> <p>We found a significant down-regulation of both <it>SEPT2 </it>and <it>MLL </it>in <it>MLL-SEPT2 </it>myeloid neoplasias. In addition, we also found that <it>MLL </it>is under-expressed in AML patients with <it>MLL </it>fusions other than <it>MLL-SEPT2</it>.</p

O alcoolismo é uma doença contagiosa? Representações sobre o contágio e a doença de ex-bebedores Is alcoholism a contagious disease? Representations on contagion and disease of ex-drinkers

Este artigo busca estabelecer os contornos de uma teoria cultural do contágio a propósito da doença alcoólica. Assim, ao contrário do modelo biomédico, que circunscreve o contágio ao âmbito biológico e fisiológico atestado clinicamente, busca-se refletir sobre as concepções do contágio ligadas a um contexto sociocultural específico, tal como o proposto pela associação de ex-bebedores dos Alcoólicos Anônimos (AA). A partir de pesquisa etnográfica realizada com familiares e membros do grupo Sapopemba de AA, localizado em bairro da periferia da cidade de São Paulo, Brasil, enfatiza-se o papel desta entidade como um espaço privilegiado para o estudo antropológico da experiência do alcoolismo, entendido como uma doença "contagiosa", a partir de um estudo das representações culturais, das práticas sociais e da (re)construção da identidade, ligadas ao par alcoolismo/doença. Com efeito, evidencia-se que, para os membros de AA e seus familiares, as possibilidades de contágio da doença alcoólica estão diretamente ligadas às representações construídas sobre o álcool e o alcoolismo, entendido como uma doença física e moral e a seus efeitos sobre o conjunto de relações sociais - familiares e profissionais -, nas quais o ex-bebedor está envolvido.<br>This article is an attempt to set the contours of a cultural theory of contagion about alcoholism. This way, instead of the biomedical model, which circumscribes contagion to the clinically confirmed biological and physiological environment, we try to reflect on the conceptions of contagion associated to a specific social and cultural context, like the one proposed by the Alcoholics Anonymous (AA) association of ex-drinkers. From the ethnographic research conducted within family in the Sapopemba group of AA, located in a neighbourhood in the outskirts of the city of São Paulo, Brazil, the role of this agency as a privileged place for anthropological study of alcoholism is stressed. Here alcoholism is viewed as a "contagious" disease, from a study on cultural representations, social practices and the (re)building of identity, linked to the alcoholism/disease couple. In fact, it becomes clear that, for AA members and your family, the possibilities of contagion of the alcoholic disease are directly linked to representations built on alcohol and alcoholism, understood as a physical and moral disease and to its effects on the whole of socials relationships - both family and professional - in which ex-drinkers are involved