RECICLANDO PAPEL, TRANSFORMANDO VIDAS: A CONEXÃO ENTRE A PRESERVAÇÃO DO MEIO AMBIENTE E A CONSCIENTIZAÇÃO SOBRE O SUICÍDIO

Todos nós sabemos que a reciclagem de papel é uma prática essencial para a preservação do meio ambiente, pois reduz o consumo de recursos naturais, diminui a emissão de poluentes e contribui para a redução da quantidade de resíduos sólidos. Resolvemos então unir ideias e também abordar temas sensíveis como o suicídio, especialmente por coincidir com o mês de setembro, mais especificadamente “setembro amarelo”, que se dedica à conscientização sobre a prevenção do suicídio. Este trabalho explora a conexão entre a reciclagem de papel e a importância de oferecer apoio a quem precise, promovendo a conscientização e a preservação tanto do ambiente quanto da saúde mental. Pretendemos demonstrar como a reciclagem de papel pode simbolizar a transformação, assim como a busca por apoio e esperança nas situações difíceis da vida. Além disso, almejamos conscientizar os visitantes sobre a importância de oferecer apoio emocional e buscar ajuda em momentos de crise. Para ilustrar os benefícios da reciclagem de papel e a conexão com mensagens de ajuda, exibiremos visualmente o processo de reciclagem, desde a coleta do papel usado até a transformação em novos produtos. Além disso, disponibilizaremos informações sobre como as pessoas podem apoiar e ajudar indivíduos que estão passando por momentos difíceis, entregando mensagens de esperança e apoio emocional. Algumas mensagens serão adicionadas nos papéis de forma oculta, usando solução com hidróxido de sódio para a escrita seguida da secagem, revelando as mensagens com a aplicação de fenolftaleína através de um borrifador. Esperamos que os visitantes da feira compreendam a importância da reciclagem de papel como uma ação tangível para a preservação do meio ambiente e como uma metáfora poderosa para a transformação pessoal. Além disso, desejamos que os participantes compreendam a relevância de discutir abertamente questões emocionais e se sensibilizem para a importância de oferecer apoio, especialmente durante o mês Setembro Amarelo. Esperamos que essa conexão entre a reciclagem e a conscientização sobre o suicídio incentive a reflexão sobre como pequenas ações individuais podem ter um impacto significativo tanto na sociedade quanto na vida das pessoas. Ao adotar a reciclagem como uma metáfora para a transformação pessoal e a busca de apoio, esperamos inspirar ações positivas e promover uma cultura de cuidado tanto com o ambiente quanto com a saúde mental

BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with IGH resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3-rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in CLL but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter 4 tumors transformed to a large B-cell lymphoma. We designed a novel FISH assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

BCR/ABL1 Fluorescence In Situ Hybridization Fusion Signals on Both Copies of Chromosome 22 in a Philadelphia-Masked Chronic Myeloid Leukemia Case: Implication for the Therapy

The cytogenetic hallmark of Chronic Myeloid Leukemia (CML) is the presence of Philadelphia (Ph) chromosome, which results from a reciprocal translocation t(9;22)(q34;q11). In this report, we describe a CML patient with no evidence of Ph chromosome but trisomy of chromosome 8 as single cytogenetic abnormality and a typical e14a2 (b3a2) BCR-ABL1 fusion transcript. Fluorescence In Situ Hybridization (FISH) analysis revealed an uncommon signal pattern: the fusion signals were located on both copies of chromosome 22. During the course of the disease the appearance of the p.(Tyr315Ile) mutation was recorded. To the best of our knowledge this is the first Ph chromosome-negative CML case with e14a2 (b3a2) BCR-ABL1 transcript and p.(Tyr315Ile) mutation

BCL3 rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

Wide-transcriptome analysis and cellularity of bone marrow CD34+/lin- cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs. 12 months of first-line nilotinib treatment

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined

Nilotinib-induced bone marrow CD34+/lin-Ph+ cells early clearance in newly diagnosed CP-Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study

none21Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph-chromosome and the BCR-ABL tyrosine-kinase (TK). Target-therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second-generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin-Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in-vivo activity and timecourse of first-line Nilotinib therapy on BM CD34+/lin-Ph+ cells clearance. Eighty-seven CP-CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin- cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per-Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin- cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK-STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed.nonePungolino, Ester; D'adda, Mariella; De Canal, Gabriella; Trojani, Alessandra; Perego, Alessandra; Elena, Chiara; Lunghi, Francesca; Turrini, Mauro; Borin, Lorenza; Iurlo, Alessandra; Latargia, Maria Luisa; Carraro, Maria Cristina; Spina, Francesco; Artale, Salvatore; Anghilieri, Michela; Molteni, Alfredo; Caramella, Marianna; Baruzzo, Giacomo; Nichelatti, Michele; Di Camillo, Barbara; Cairoli, RobertoPungolino, Ester; D'Adda, Mariella; De Canal, Gabriella; Trojani, Alessandra; Perego, Alessandra; Elena, Chiara; Lunghi, Francesca; Turrini, Mauro; Borin, Lorenza; Iurlo, Alessandra; Latargia, Maria Luisa; Carraro, Maria Cristina; Spina, Francesco; Artale, Salvatore; Anghilieri, Michela; Molteni, Alfredo; Caramella, Marianna; Baruzzo, Giacomo; Nichelatti, Michele; Di Camillo, Barbara; Cairoli, Robert

Nilotinib interferes with cell cycle, ABC transporters and JAK-STAT signaling pathway in CD34+/lin- cells of patients with chronic phase chronic myeloid leukemia after 12 months of treatment

Chronic myeloid leukemia (CML) is characterized by the constitutive tyrosine kinase activity of the oncoprotein BCR-ABL1 in myeloid progenitor cells that activates multiple signal transduction pathways leading to the leukemic phenotype. The tyrosine-kinase inhibitor (TKI) nilotinib inhibits the tyrosine kinase activity of BCR-ABL1 in CML patients. Despite the success of nilotinib treatment in patients with chronic-phase (CP) CML, a population of Philadelphia-positive (Ph+) quiescent stem cells escapes the drug activity and can lead to drug resistance. The molecular mechanism by which these quiescent cells remain insensitive is poorly understood. The aim of this study was to compare the gene expression profiling (GEP) of bone marrow (BM) CD34+/lin- cells from CP-CML patients at diagnosis and after 12 months of nilotinib treatment by microarray, in order to identify gene expression changes and the dysregulation of pathways due to nilotinib action. We selected BM CD34+/lin- cells from 78 CP-CML patients at diagnosis and after 12 months of first-line nilotinib therapy and microarray analysis was performed. GEP bioinformatic analyses identified 2,959 differently expressed probes and functional clustering determined some significantly enriched pathways between diagnosis and 12 months of nilotinib treatment. Among these pathways, we observed the under expression of 26 genes encoding proteins belonging to the cell cycle after 12 months of nilotinib treatment which led to the up-regulation of chromosome replication, cell proliferation, DNA replication, and DNA damage checkpoint at diagnosis. We demonstrated the under expression of the ATP-binding cassette (ABC) transporters ABCC4, ABCC5, and ABCD3 encoding proteins which pumped drugs out of the cells after 12 months of nilotinib. Moreover, GEP data demonstrated the deregulation of genes involved in the JAK-STAT signaling pathway. The down-regulation of JAK2, IL7, STAM, PIK3CA, PTPN11, RAF1, and SOS1 key genes after 12 months of nilotinib could demonstrate the up-regulation of cell cycle, proliferation and differentiation via MAPK and PI3K-AKT signaling pathways at diagnosis