1,721,081 research outputs found
Role of nucleophosmin in acute myeloid leukemia
No full textNucleophosmin (NPM) is a nucleolar phosphoprotein implicated in the regulation of multiple cellular functions, which possesses both oncogenic and tumor-suppressor properties. Mutations of the NPM1 gene leading to the expression of a cytoplasmic mutant protein, NPMc+, are the most frequent genetic abnormalities found in acute myeloid leukemias. Acute myeloid leukemias with mutated NPM1 have distinct characteristics, including a significant association with a normal karyotype, involvement of different hematopoietic lineages, a specific gene-expression profile and clinically, a better response to induction therapy and a favorable prognosis. NPMc+ maintains the capacity of wild-type NPM to interact with a variety of cellular proteins, and impairs their activity by delocalizing them to the cytoplasm. In this review we summarize recent discoveries concerning NPM function, and discuss their possible impact on the pathogenesis of acute myeloid leukemias with mutated NPM
Nucleophosmin and its complex network : a possible therapeutic target in hematological diseases
No full textNucleophosmin (NPM, also known as B23, numatrin or NO38) is a ubiquitously expressed phosphoprotein belonging to the nucleoplasmin family of chaperones. NPM is mainly localized in the nucleolus where it exerts many of its functions, but a proportion of the protein continuously shuttles between the nucleus and the cytoplasm. A growing number of cellular proteins have been described as physical interactors of NPM, and consequently, NPM is thought to have a relevant role in diverse cellular functions, including ribosome biogenesis, centrosome duplication, DNA repair and response to stress. NPM has been implicated in the pathogenesis of several human malignancies and intriguingly, it has been described both as an activating oncogene and a tumor suppressor, depending on cell type and protein levels. In fact, increased NPM expression is associated with different types of solid tumors whereas an impairment of NPM function is characteristic of a subgroup of hematolologic malignancies. A large body of experimental evidence links the deregulation of specific NPM functions to cellular transformation, yet the molecular mechanisms through which NPM contributes to tumorigenesis remain elusive. In this review, we have summarized current knowledge concerning NPM functions, and attempted to interpret its multifaceted and sometimes apparently contradictory activities in the context of both normal cellular homeostasis and neoplastic transformation
Nuclear protein pirin negates the cellular senescence barrier against cancer development
No full textPirin (PIR) is a highly conserved protein whose biological role has not yet been fully elucidated. Several studies reported its involvement in cancer progression, proposing a function in apoptosis. We have shown that PIR is primarily expressed in melanocytes and melanoma cells and displays a complex pattern of expression and localization. High levels of PIR protein are found in normal melanocytes whereas low or undetectable levels are present in nevi. Additionally, PIR expression is found in a subset of melanoma cases with increasing levels correlating with tumor progression. Knock-down experiments performed in melanoma cells with high PIR expression have shown a role for PIR in controlling cellular senescence. In this model, PIR ablation results in impairment of cell proliferation, morphological changes characteristic of cellular senescence and expression of senescence markers. Furthermore, oncogene activation and other senescence stimuli induce PIR downregulation. Based on our data, we propose here two alternative models to explain PIR expression pattern in nevi and melanoma and its involvement in the control of senescence. We propose that PIR plays a prominent role in negatively controlling senescence in melanocytic cells and that it could represent a novel marker for melanoma progression and a potential therapeutic target
MyWEST : my Web Extraction Software Tool for effective mining of annotations from web-based databanks
No full textMOTIVATION: High-throughput technologies create the necessity to mine large amounts of gene annotations from diverse databanks, and to integrate the resulting data. Most databanks can be interrogated only via Web, for a single gene at a time, and query results are generally available only in the HTML format. Although some databanks provide batch retrieval of data via FTP, this requires expertise and resources for locally reimplementing the databank. RESULTS: We developed MyWEST, a tool aimed at researchers without extensive informatics skills or resources, which exploits user-defined templates to easily mine selected annotations from different Web-interfaced databanks, and aggregates and structures results in an automatically updated database. Using microarray results from a model system of retinoic acid-induced differentiation, MyWEST effectively gathered relevant annotations from various biomolecular databanks, highlighted significant biological characteristics and supported a global approach to the understanding of complex cellular mechanisms. AVAILABILITY: MyWEST is freely available for non-profit use at http://www.medinfopoli.polimi.it/MyWEST
The meaning of it all: web-based resources for large-scale functional annotation and visualization of DNA microarray data
No full textThe vast amount of unstructured data emerging from the various genome projects has led to the development of a number of web-based tools designed to annotate genes with biological information. Here we discuss a selection of these tools with regards to their scope, limitations and ease of use
Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation
No full textTerminal differentiation of blood cells requires the concerted action of a series of transcription factors that are expressed at specific stages of maturation and function in a cell-type and dosage-dependent manner. Leukemogenic oncoproteins block differentiation by subverting the normal transcriptional status of hematopoietic precursor cells. Pirin (PIR) is a putative transcriptional regulator whose expression is silenced in cells bearing the acute myeloid leukemia-1 eight-twenty-one (AML1/ETO) and promyelocytic leukemia/retinoic acid receptor (PML/RAR) leukemogenic fusion proteins. A role for PIR in myeloid differentiation has not to date been reported. In this study we show that PIR expression is significantly repressed in a large proportion of acute myeloid leukemias (AMLs), regardless of subtype or underlying karyotypic abnormalities. We show that PIR expression increases during in vitro myeloid differentiation of primary hematopoietic precursor cells, and that ablation of PIR in the U937 myelomonocytic cell line or in murine primary hematopoietic precursor cells results in impairment of terminal myeloid differentiation. Gene expression profiling of U937 cells after knockdown of PIR revealed increased expression of genes associated with the early phases of hematopoiesis, in particular, homeobox A (HOXA) genes. Our results suggest that PIR is required for terminal myeloid maturation, and its downregulation may contribute to the differentiation arrest associated with AM
Understanding the molecular basis of acute myeloid leukemias : where are we now?
No full textAlthough the treatment modalities for acute myeloid leukemia (AML) have not changed
much over the past 40 years, distinct progress has been made in deciphering the basic
biology underlying the pathogenesis of this group of hematological disorders. Studies show
that AML development is a multicause, multistep and multipathway process. Accordingly,
AMLs constitute a heterogeneous group of diseases. The thorough understanding of the
molecular basis of AML is paving the way for better therapeutic approaches. Multiple
novel drugs are being introduced and new, more efficient and less toxic formulations of
conventional therapeutics are becoming available. Here, we review the recent advances
in the comprehension of the molecular processes that lead to the onset of AML and its
translation into clinical practice
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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