Anonáceas provocam mortalidade em larvas de Aedes aegypti (Linnaeus, 1762) (Diptera:Culicidae)

This work aimed at to evaluate the effect biocidal of Annona crassiflora, A. dioica, A. mucosa, A. coriacea and Cardiopetalum calophyllum in different solvents on larvae of A. aegypti after 24 hours of exhibition, being the data submitted to the variance analysis and test of comparison of averages. The lethal concentration (LC50) it was certain for Probit. A. coriacea in methanol and hexano and A. mucosa in methanol presented 100% of mortality in 0,1mg/mL, with LC50 0.007, 0.007 and 0.010, respectively. A. crassiflora presented superior mortality to 90% in 1.0 mg/mL, in the extract rude methanolic (CL50 0.100), hexane (LC50 0.507), dichloromethane (LC50 0.185) and in the fraction hexane (CL50 0.433). The fractions hidroalcoolica, etila acetate and chloroform didn’t cause mortality. In the species A. dioica and C. calophyllum the mortality was subscript to 50%. Therefore, A. crassiflora, A. coriacea and A. mucosa, in the solvents methanol and hexane are promising species for the development of futures biocides in the combat to the dengue vector.Este trabalho teve por objetivo avaliar o efeito biocida de Annona crassiflora, A. dioica, A. mucosa, A. coriacea e Cardiopetalum calophyllum sobre larvas de A. aegypti. As concentrações testadas foram 1,0, 0,8, 0,6, 0,5, 0,2, 0,1 mg/mL, para extratos brutos e/ou frações de A. crassiflora, A. dioica e C. calophyllum e 0,1, 0,08, 0,05, 0,02 e 0,01 mg/mL, para os extratos brutos de A. mucosa e A. coriacea.  Em cada solução foram adicionadas 20 larvas de 3° estádio de A. aegypti e a mortalidade larval foi registrada após 24 horas de exposição aos tratamentos e os dados submetidos à análise de variância e teste de comparação de médias. A concentração letal (CL50) foi determinada por Probit. A. coriacea em metanol e hexano e A. mucosa em metanol apresentaram 100% de mortalidade em 0,1 mg/mL. A. crassiflora apresentou mortalidade superior a 90% em 1,0 mg/mL, no extrato bruto metanólico, hexânico, diclorometano e na fração hexânica. As frações hidroalcóolica, acetato de etila e clorofórmio não apresentaram atividade inseticida. Nas espécies A. dioica e C. calophyllum com extrato bruto a mortalidade foi inferior a 50%. Portanto, A. crassiflora, A. coriacea e A. mucosa em metanol e hexano são promissoras no desenvolvimento de futuros biocidas, para o controle do vetor da dengue

A novel PAX5 rearrangement in TCF3-PBX1 acute lymphoblastic leukemia: a case report

Abstract Background Chromosome translocations are a hallmark of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Additional genomic aberrations are also crucial in both BCP-ALL leukemogenesis and treatment management. Herein, we report the phenotypic and molecular cytogenetic characterization of an extremely rare case of BCP-ALL harboring two concomitant leukemia-associated chromosome translocations: t(1;19)(q23;q13.3) and t(9;17)(p13;q11.2). Of note, we described a new rearrangement between exon 6 of PAX5 and a 17q11.2 region, where intron 3 of SPECC1 is located. This rearrangement seems to disrupt PAX5 similarly to a PAX5 deletion. Furthermore, a distinct karyotype between diagnosis and relapse samples was observed, disclosing a complex clonal evolution during leukemia progression. Case presentation A 16-year-old boy was admitted febrile with abdominal and joint pain. At clinical investigation, he presented with anemia, splenomegaly, low white blood cell count and 92% lymphoblast. He was diagnosed with pre-B ALL and treated according to high risk GBTLI-ALL2009. Twelve months after complete remission, he developed a relapse in consequence of a high central nervous system and bone marrow infiltration, and unfortunately died. Conclusions To our knowledge, this is the first report of a rearrangement between PAX5 and SPECC1. The presence of TCF3-PBX1 and PAX5-rearrangement at diagnosis and relapse indicates that both might have participated in the malignant transformation disease maintenance and dismal outcome

ARID5B polymorphism confers an increased risk to acquire specific MLL rearrangements in early childhood leukemia

Background: Acute leukemia in early age (EAL) is characterized by acquired genetic alterations such as MLL rearrangements (MLL-r). The aim of this case-controlled study was to investigate whether single nucleotide polymorphisms (SNPs) of IKZF1, ARID5B, and CEBPE could be related to the onset of EAL cases (<24 months-old at diagnosis). Methods: The SNPs (IKZF1 rs11978267, ARID5B rs10821936 and rs10994982, CEBPE rs2239633) were genotyped in 265 cases [169 acute lymphoblastic leukemia (ALL) and 96 acute myeloid leukaemia (AML)] and 505 controls by Taqman allelic discrimination assay. Logistic regression was used to evaluate the association between SNPs of cases and controls, adjusted on skin color and/or age. The risk was determined by calculating odds ratios (ORs) with 95% confidence interval (CI). Results: Children with the IKZF1 SNP had an increased risk of developing MLL-germline ALL in white children. The heterozygous/mutant genotype in ARID5B rs10994982 significantly increased the risk for MLL-germline leukemia in white and non-white children (OR 2.60, 95% CI: 1.09-6.18 and OR 3.55, 95% CI: 1.57-8.68, respectively). The heterozygous genotype in ARID5B rs10821936 increased the risk for MLL-r leukemia in both white and non-white (OR 2.06, 95% CI: 1.12-3.79 and OR 2.36, 95% CI: 1.09-5.10, respectively). Furthermore, ARID5B rs10821936 conferred increased risk for MLL-MLLT3 positive cases (OR 7.10, 95% CI:1.54-32.68). Our data do not show evidence that CEBPE rs2239633 confers increased genetic susceptibility to EAL. Conclusions: IKZF1 and CEBPE variants seem to play a minor role in genetic susceptibility to EAL, while ARID5B rs10821936 increased the risk of MLL-MLLT3. This result shows that genetic susceptibility could be associated with the differences regarding MLL breakpoints and partner genes

COBL is a novel hotspot for IKZF1 deletions in childhood acute lymphoblastic leukemia

IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in childhood B-cell precursor acute lymphoblastic leukemia. Because of its clinical importance, we previously mapped breakpoints of intragenic deletions and developed a multiplex PCR assay to detect recurrent intragenic ΔIKZF1. Since the multiplex PCR was not able to detect complete deletions (IKZF1 Δ1-8), which account for ~30% of all ΔIKZF1, we aimed at investigating the genomic scenery of IKZF1 Δ1-8. Six samples of cases with IKZF1 Δ1-8 were analyzed by microarray assay, which identified monosomy 7, isochromosome 7q, and large interstitial deletions presenting breakpoints within COBL gene. Then, we established a multiplex ligation-probe amplification (MLPA) assay and screened copy number alterations within chromosome 7 in 43 diagnostic samples with IKZF1 Δ1-8. Our results revealed that monosomy and large interstitial deletions within chromosome 7 are the main causes of IKZF1 Δ1-8. Detailed analysis using long distance inverse PCR showed that six patients (16%) had large interstitial deletions starting within intronic regions of COBL at diagnosis, which is ~611 Kb downstream of IKZF1, suggesting that COBL is a hotspot for ΔIKZF1. We also investigated a series of 25 intragenic deletions (Δ2–8, Δ3–8 or Δ4–8) and 24 relapsed samples, and found one IKZF1-COBL tail-to-tail fusion, thus supporting that COBL is a novel hotspot for ΔIKZF1. Finally, using RIC score methodology, we show that breakpoint sequences of IKZF1 Δ1-8 are not analog to RAG-recognition sites, suggesting a different mechanism of error promotion than that suggested for intragenic ΔIKZF1

COBL is a novel hotspot for IKZF1 deletions in childhood acute lymphoblastic leukemia

IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in childhood B-cell precursor acute lymphoblastic leukemia. Because of its clinical importance, we previously mapped breakpoints of intragenic deletions and developed a multiplex PCR assay to detect recurrent intragenic ΔIKZF1. Since the multiplex PCR was not able to detect complete deletions (IKZF1 Δ1-8), which account for ~30% of all ΔIKZF1, we aimed at investigating the genomic scenery of IKZF1 Δ1-8. Six samples of cases with IKZF1 Δ1-8 were analyzed by microarray assay, which identified monosomy 7, isochromosome 7q, and large interstitial deletions presenting breakpoints within COBL gene. Then, we established a multiplex ligation-probe amplification (MLPA) assay and screened copy number alterations within chromosome 7 in 43 diagnostic samples with IKZF1 Δ1-8. Our results revealed that monosomy and large interstitial deletions within chromosome 7 are the main causes of IKZF1 Δ1-8. Detailed analysis using long distance inverse PCR showed that six patients (16%) had large interstitial deletions starting within intronic regions of COBL at diagnosis, which is ~611 Kb downstream of IKZF1, suggesting that COBL is a hotspot for ΔIKZF1. We also investigated a series of 25 intragenic deletions (Δ2–8, Δ3–8 or Δ4–8) and 24 relapsed samples, and found one IKZF1-COBL tail-to-tail fusion, thus supporting that COBL is a novel hotspot for ΔIKZF1. Finally, using RIC score methodology, we show that breakpoint sequences of IKZF1 Δ1-8 are not analog to RAG-recognition sites, suggesting a different mechanism of error promotion than that suggested for intragenic ΔIKZF1

Intragenic amplification of PAX5: a novel subgroup in B-cell precursor acute lymphoblastic leukemia?

Intragenic PAX5 amplification defines a novel, relapse-prone subtype of B-cell precursor acute lymphoblastic leukemia with a poor outcome