RESUMO
Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for "Differentially Expressed Genes" (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.
Assuntos
Biomarcadores Tumorais/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Quinase 6 Dependente de Ciclina/genética , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Rearranjo Gênico , Histona-Lisina N-Metiltransferase/genética , Humanos , Lactente , Recém-Nascido , Masculino , Família Multigênica , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Falha de TratamentoAssuntos
Leucemia Mielomonocítica Aguda , Mutação , Proteína de Leucina Linfoide-Mieloide , Proteínas de Fusão Oncogênica , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Lactente , Leucemia Mielomonocítica Aguda/genética , Leucemia Mielomonocítica Aguda/metabolismo , Masculino , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismoRESUMO
BACKGROUND: To identify the predictive factors for malignancies using basic clinical and laboratory information in children presenting with musculoskeletal pain and eventually diagnosed with juvenile idiopathic arthritis (JIA) or malignancy. METHODS: A retrospective case-control chart review research examining laboratory data from patients referred for musculoskeletal pain in 2001-2010 and diagnosed with malignancy or JIA was performed. The validity of each test for the diagnosis of neoplasia was assessed by calculating the sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and likelihood ratios. RESULTS: A total of 134 patients were enrolled. Statistically significant differences were found in neutrophil count, Hb, LDH, IgA and C4 values, ANA, anti-EA EBV IgG and anti-CMV IgG titres. High LDH value and anti-CMV IgG were the most predictive factors for neoplasia. High specificity factors for neoplasia were abnormal values of neutrophil count, Hb, IgA and C4, and the presence of anti-EA EBV and anti-CMV IgG. High PPV were recorded for abnormal neutrophil count, Hb value and anti-CMV titre. A low NPV was found only for anti-EA EBV and anti-CMV titres. CONCLUSIONS: In this setting of patients, minimum changes in neutrophil count, particularly if associated with low Hb and high LDH levels, are to be thoroughly considered, because they appear as the most predictive factors for the diagnosis of tumour.
Assuntos
Artrite Juvenil/diagnóstico , Biomarcadores Tumorais/sangue , Leucemia Mieloide Aguda/diagnóstico , Linfoma/diagnóstico , Dor Musculoesquelética/etiologia , Neutrófilos/metabolismo , Adolescente , Artrite Juvenil/sangue , Artrite Juvenil/complicações , Estudos de Casos e Controles , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/complicações , Contagem de Leucócitos , Funções Verossimilhança , Linfoma/sangue , Linfoma/complicações , Masculino , Dor Musculoesquelética/sangue , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
In this paper different topologies of populations of FitzHugh-Nagumo neurons have been introduced in order to investigate the role played by the noise in the network. Each neuron is subjected to an independent source of noise. In these conditions the behavior of the population depends on the connection among the elements. By analyzing several kinds of topology (ranging from regular to random) different behaviors have been observed. Several topologies behave in an optimal way with respect to the range of noise level leading to an improvement in the stimulus response coherence, while others with respect to the maximum values of the performance index. However, the best results in terms of both the suitable noise level and high stimulus response coherence have been obtained when a diversity in neuron characteristic parameters has been introduced and the neurons have been connected in a small-world topology.