RESUMEN
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.
Asunto(s)
Biomarcadores de Tumor/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Proteínas de Complejo Poro Nuclear/genética , Adolescente , Niño , Preescolar , Estudios de Cohortes , Quinasa 6 Dependiente de la Ciclina/genética , Femenino , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Reordenamiento Génico , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Lactante , Recién Nacido , Masculino , Familia de Multigenes , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Insuficiencia del TratamientoRESUMEN
Despite a high cure rate in childhood BCP-ALL, 20% of children still presents with relapse, mostly due to a persistent leukemic clone during the first-line treatment. In this context, obtaining a molecular remission is crucial for reaching a successful allogeneic hematopoietic stem cell transplantation. Bortezomib was effectively administered to children with resistant/relapsed (r/r) BCP-ALL. Moreover, high risk ALL is characterized by the increasing expression of CD20. For the first time we reported two children with r/r BCP-ALL who received a treatment schema including Bortezomib and Rituximab, achieving morphological and molecular remission. Children with high risk features, such as persistent minimal residual disease during induction, will benefit from this combination. Is it time to move toward the first line?
Asunto(s)
Bortezomib/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Rituximab/administración & dosificación , Aloinjertos , Niño , Humanos , MasculinoRESUMEN
Nutrition has a central role in child growth with long-term effects, and nutrition management in gastrointestinal disorders has great importance for child health and disease outcomes. Breast milk is the first choice for infant nutrition. When it is not available, special milk formulas are adopted in specific conditions, as a medical treatment. Moving from the strong guidelines, recommendations and the new possibilities of special diet treatment, this review will analyse the current diet treatment in different gastrointestinal disorders, including food allergy, cystic fibrosis, inflammatory bowel diseases, short-bowel syndrome, gastroesophageal reflux, and eosinophilic esophagitis. The review also aimed at understanding the role of diet and its effects on these diseases. The growth monitoring can prevent malnutrition and improve disease outcomes, particularly in children, and an appropriate dietary management targeted to specific disorders is the best therapeutic choice alone or in combination with pharmacological therapy.
Asunto(s)
Esofagitis Eosinofílica , Hipersensibilidad a los Alimentos , Gastritis , Reflujo Gastroesofágico , Niño , Esofagitis Eosinofílica/diagnóstico , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/prevención & control , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/prevención & control , Humanos , LactanteRESUMEN
The aim of precision medicine is setting up targeted therapies for selected patients that would ideally have high effectiveness and few side effects. This is made possible by targeted therapy drugs that selectively act on a specific pathway. Precision medicine is spreading to many medical specialties, and there is increasing interest in the context of allergic airway diseases, such as allergic rhinitis, chronic rhinosinusitis, and asthma. This review is an update of new targets in the treatment of childhood allergic upper airway diseases and asthma, including the most recent biologic drugs that have already been licensed or are in the pipeline to be tested with children.
RESUMEN
During the last several years, the interest in the role of microbiota in human health has grown significantly. For many years, the lung was considered a sterile environment, and only recently, with the use of more sophisticated techniques, has it been demonstrated that colonization by a complex population of microorganisms in lower airways also occurs in healthy subjects; a predominance of some species of Proteobacteria, Firmicutes, and Bacteroidetes phyla and with a peculiar composition in some disease conditions, such as asthma, have been noted. Lung microbiota derives mainly from the higher airways microbiota. Although we have some information about the role of gut microbiota in modulation of immune system, less it is known about the connection between lung microbiota and local and systemic immunity. There is a correlation between altered microbiota composition and some diseases or chronic states; however, despite this correlation, it has not been clearly demonstrated whether the lung microbiota dysbiosis could be a consequence or a cause of these diseases. We are far from a scientific approach to the therapeutic use of probiotics in airway diseases, but we are only at the starting point of a knowledge process in this fascinating field that could reveal important surprises, and randomized prospective studies in future could reveal more about the clinical possibilities for controlling lung microbiota. This review was aimed at updating the current knowledge in the field of airway microbiota.