BackgroundMicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.0) of purified tumor (CD138+) cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 controls.ResultsUnsupervised cluster analysis revealed that MM and MGUS samples have a distinct microRNA expression profile from control CD138+ cells. The majority of microRNAs aberrantly expressed in MM (109/129) were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell malignancies revealed a surprising degree of similarity (~40%) suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59%) of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14) and t(11;14)) and del(13q). Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis) and correctly predicted these abnormalities in > 85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS) in MM, ten of which were significant by univariate (logrank) survival analysis.ConclusionsIn summary, this work has identified aberrantly expressed microRNAs associated with the diagnosis, pathogenesis and prognosis of MM, data which will prove an invaluable resource for understanding the role of microRNAs in this devastating disease.ReviewersThis article was reviewed by Prof. Neil Smalheiser, Prof. Yuriy Gusev, and an unknown reviewer.
Children are at high risk of developing active disease after exposure to TB. The study describes the minimal symptoms manifested in many of the children with significant radiological changes consistent with pulmonary TB. This highlights the need to consider Mantoux testing and chest X-rays for children presenting with persistent respiratory symptoms in high-risk populations. Issues of contact tracing and adherence were also a problem in this population.
Key content An overview is given of the different types of haemoglobinopathies and the effect of iron overload on the function of vital organs, including the endocrine system. Assessment modalities for ovarian and testicular function measurement. Current management options for patients with hypogonadotrophic hypogonadism secondary to iron overload include chelation therapy from an early age and human menopausal gonadotrophin to induce ovulation and spermatogenesis. Egg, sperm or embryo donation remain alternative options in cases refractory to stimulation protocols. Cryopreservation is an option to retain future fertility in some patients with a haemoglobinopathy, but is not standard care. We consider the psychological impact of a haemoglobinopathy and iron overload, and their effects on reproductive health, as well as good medical support by a multidisciplinary team. Learning objectives To understand the current evidence of the impact of iron overload secondary to a haemoglobinopathy on reproductive health. To evaluate best practice and alternative options in the management of patients with iron overload in a reproductive health setting.
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