A novel spliced fusion of MLL with CT45A2 in a pediatric biphenotypic acute leukemia

Background: Abnormalities of 11q23 involving the MLL gene are found in approximately 10% of human leukemias. To date, nearly 100 different chromosome bands have been described in rearrangements involving 11q23 and 64 fusion genes have been cloned and characterized at the molecular level. In this work we present the identification of a novel MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia. Methods: Cytogenetics, fluorescence in situ hybridization (FISH), molecular studies (RT-PCR and LDI-PCR), and bioinformatic sequence analysis were used to characterize the CT45A2 gene as novel MLL fusion partner in pediatric acute leukemia. Results: Fluorescence in situ hybridization of the patient G-banded metaphases demonstrated a cryptic insertion of 11q23 in Xq26.3 involving the MLL gene. Breakpoint fusion analysis revealed that a DNA fragment of 653 kb from 11q23, containing MLL exons 1-9 in addition to 16 other 11q23 genes, was inserted into the upstream region of the CT45A2 gene located at Xq26.3. In addition, a deletion at Xq26.3 encompassing the 3' region of the DDX26B gene (exons 9-16) and the entire CT45A1 gene was identified. RNA analysis revealed the presence of a novel MLL-CT45A2 fusion transcript in which the first 9 exons of the MLL gene were fused in-frame to exon 2 of the CT45A2 gene, resulting in a spliced MLL fusion transcript with an intact open reading frame. The resulting chimeric transcript predicts a fusion protein where the N-terminus of MLL is fused to the entire open reading frame of CT45A2. Finally, we demonstrate that all breakpoint regions are rich in long repetitive motifs, namely LINE/L1 and SINE/Alu sequences, but all breakpoints were exclusively identified outside these repetitive DNA sequences. Conclusion: We have identified CT45A2 as a novel spliced MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia, as a result of a cryptic insertion of 11q23 in Xq26.3. Since CT45A2 is the first Cancer/Testis antigen family gene found fused with MLL in acute leukemia, future studies addressing its biologic relevance for leukemogenesis are warranted

The state of research into children with cancer across Europe : new policies for a new decade

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.peer-reviewe

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

Soil macrofauna communities in Brazilian land-use systems

Soil animal communities include more than 40 higher-order taxa, representing over 23% of all described species. These animals have a wide range of feeding sources and contribute to several important soil functions and ecosystem services. Although many studies have assessed macroinvertebrate communities in Brazil, few of them have been published in journals and even fewer have made the data openly available for consultation and further use. As part of ongoing efforts to synthesise the global soil macrofauna communities and to increase the amount of openly-accessible data in GBIF and other repositories related to soil biodiversity, the present paper provides links to 29 soil macroinvertebrate datasets covering 42 soil fauna taxa, collected in various land-use systems in Brazil. A total of 83,085 georeferenced occurrences of these taxa are presented, based on quantitative estimates performed using a standardised sampling method commonly adopted worldwide to collect soil macrofauna populations, i.e. the TSBF (Tropical Soil Biology and Fertility Programme) protocol. This consists of digging soil monoliths of 25 x 25 cm area, with handsorting of the macroinvertebrates visible to the naked eye from the surface litter and from within the soil, typically in the upper 0-20 cm layer (but sometimes shallower, i.e. top 0-10 cm or deeper to 0-40 cm, depending on the site). The land-use systems included anthropogenic sites managed with agricultural systems (e.g. pastures, annual and perennial crops, agroforestry), as well as planted forests and native vegetation located mostly in the southern Brazilian State of Paraná (96 sites), with a few additional sites in the neighbouring states of São Paulo (21 sites) and Santa Catarina (five sites). Important metadata on soil properties, particularly soil chemical parameters (mainly pH, C, P, Ca, K, Mg, Al contents, exchangeable acidity, Cation Exchange Capacity, Base Saturation and, infrequently, total N), particle size distribution (mainly % sand, silt and clay) and, infrequently, soil moisture and bulk density, as well as on human management practices (land use and vegetation cover) are provided. These data will be particularly useful for those interested in estimating land-use change impacts on soil biodiversity and its implications for below-ground foodwebs, ecosystem functioning and ecosystem service delivery.Quantitative estimates are provided for 42 soil animal taxa, for two biodiversity hotspots: the Brazilian Atlantic Forest and Cerrado biomes. Data are provided at the individual monolith level, representing sampling events ranging from February 2001 up to September 2016 in 122 sampling sites and over 1800 samples, for a total of 83,085 ocurrences

Sarcoma de Ewing ou Linfoma Ósseo

Apresenta-se o caso clínico de uma criança de 4 anos, sexo masculino com história de dor no membro inferior direito, claudicação da marcha e exame objectivo sem outras alterações. Oa exames imagiológicos mostraram uma lesão osteolítica desde o colo até ao terço distai da diáfise femural. O doente foi referenciado para a nossa Instituição com o diagnóstico provável de Sarcoma de Ewing versus linfoma, Com o objectivo de estadiar o tumor foi realizada uma tomografia axial computorizada (TAC) abdominal que revelou uma massa sólida intra-renal á esquerda. Foram realizadas duas biópsias (fémur e rim) que confirmaram o diagnóstico de linfoma linfoblástico de células da linhagem B. Este caso demonstra que o diagnóstico de linfoma ósseo deve ser incluído no grupo de diagnósticos diferenciais de tumores ósseos, ainda que a ocorrência deste tipo de tumor numa criança seja rara.Palavras-Chave - Tumor ósseo, linfoma de células   sarcoma de Ewin

Síndroma de Lise Tumoral. Fisiopatologia e Tratamento

O síndrome de lise tumoral engloba um conjunto de alterações metabólicas — hiperuricemia, hiperfosfatemia, hipocalcemia, hipercaliemia e uremia — que ocorrem como consequência da lise celular, espontânea ou induzida por quimioterapia, em associação com doenças malignas linfoproliferativas.Apresenta-se a fisiopatologia e patogénese do síndrome e a mais actual abordagem de prevenção e terapêutica

Hístiocitose de Células de Langerhans: uma Doença - Várias Apresentações

A Histíocitose das células de Langerhans, anteriormente conhecida como Hístiocitose X, é uma doença rara, de etiologia desconhecida e que afecta 2 a 5 crianças por milhão, por ano. Esta doença consiste na proliferação e disseminação de células com característicasparticulares, entre as quais se destacam os grânulos de Birbeck intracitoplasmátícos, a expressão do antigénio de superfície CD la e a expressão citoplasmática e nuclear de proteína SlOO, próprias de células apresentadoras de antigénios no território cutâneo. A história natural varia entre uma doença benigna cora resolução espontânea e uma doença progressiva fatal. Os três casos de hístiocitose de células de Langerhans que descrevemos evidenciam a diversidade de apresentação e evolução desta doença.Palavras-Chave: Hístiocitose, Células de Langerhans; Diagnóstico; Prognóstico; Tratamento

Anemias Hereditárias

Os autores efectuam a revisão das anemias hereditárias da consulta de hematologia pediátrica do Hospital S. João no período compreendido entre 1982 e 1995. Dividem-nas em três grandes grupos: Hemoglobinopatias, Doenças da Membrana do glóbulo rubro e Enzimopatias. Calculam a sua frequência relativa, os parâmetros clínicos e analíticos relevantes no diagnóstico, a abordagem terapêutica e respectiva evolução.Destacam a especificidade desta consulta em que as anemias hereditárias correspondem a 47,8% dos 205 casos de anemia observados. As hemoglobinopatias são a patologia mais frequente (51,2%), com franco predomínio dos portadores heterozigotos de 3-talassemia (85%). No grupo das membranopatias, a esferocitose hereditária constitui 97,3% dos casos.Fazem algumas considerações sobre anemias hereditárias e comparam os resultados obtidos com os de publicações relativas à sua prevalência no país. Salientam a importância do diagnóstico precoce dos doentes e portadores, e do aconselhamento genético do casal de risco no sentido da diminuição da incidência e da morbilidade destas patologias