1,721,051 research outputs found
From bone marrow failure syndromes to VEXAS: Disentangling clonal hematopoiesis, immune system, and molecular drivers
No full textClonal hematopoiesis (CH) is a result of the selective expansion of hematopoietic stem and progenitor cells
(HSPCs) carrying somatic mutations originating from a primary HSC. The advent of modern genomic technologies has helped recognizing that CH is common in elderly healthy subjects as a result of the aging bone marrow
(BM). CH in healthy subjects without abnormalities in blood counts is known as CH of indeterminate potential.
CH is also seen in BM failure (BMF) disorders. Whether CH alarms for the risk to develop malignant evolution in
BMF or creates an adaptation to selective pressure is a matter of controversy. As such, a continuum might exist
from pre-malignant to malignant hematopoietic diseases. This review summarizes how somatic mutations and
immune derangement in HSCs shape disease evolution and describes the complexity of disorders such as VEXAS
as the prototypic tetrad of somatic mutations, morphologic features, inflammatory pathways and immune
overshooting. In such a view, we interconnect the axis aging and immune-hematopoietic system, which all
convey important clues for the risk to develop malignancies
Dissecting the genomic traits and clinical course of secondary myelodysplastic syndrome following aplastic anaemia: A milestone
No full textDissecting the genomic traits and clinical course of secondary myelodysplastic syndrome following aplastic anaemia is a milestone. The report by Li and colleagues investigates determinants of evolution to myelodysplastic syndrome and acute myeloid leukaemia in patients with aplastic anaemia and paroxysmal nocturnal haemoglobinuria with a specific focus on post-transplant outcomes. Commentary on: Li et al. Clinical and genetic profiles and outcomes of allogeneic haematopoietic stem cell transplantation in secondary myelodysplastic syndrome following aplastic anaemia
Soluble and cleaved forms of the urokinase-receptor: degradation products or active molecules?
No full textThe urokinase-mediated plasminogen activation (PA) system is involved in many physiological and pathological events that include cell migration and tissue remodelling, such as embryogenesis, ovulation, inflammation, wound healing, angiogenesis and tumor invasion and metastasis. The urokinase receptor (uPAR) is a key molecule of this system and can bind extracellular and cell membrane molecules such as urokinase (uPA), vitronectin (VN), integrins and chemotaxis receptors. These multiple interactions can be modulated by the shedding or the cleavage of the cell membrane receptor. Indeed, cleaved forms of uPAR, lacking the N-terminal D1 domain, have been detected on the surface of cells and in tissues, while soluble forms have been found in biological fluids. Cleaved and soluble forms could represent the intermediary products of the uPAR metabolism or active molecules with precise and distinct functional roles.
Here, we review the data concerning the in vitro and in vivo identification of these uPAR forms, their origin and functions, and the role that uPAR shedding and cleavage could play in biological processes
From bench to bedside and beyond: Therapeutic scenario in acute myeloid leukemia
No full textAcute myeloid leukemia (AML) is a heterogeneous group of clonal disorders characterized by abnormal proliferation of undifferentiated myeloid progenitors, impaired hematopoiesis, and variable response to therapy. To date, only about 30% of adult patients with AML become long-term survivors and relapse and/or disease refractoriness are the major cause of treatment failure. Thus, this is an urgent unmet clinical need and new drugs are envisaged in order to ameliorate disease survival outcomes. Here, we review the latest therapeutic approaches (investigational and approved agents) for AML treatment. A specific focus will be given to molecularly targeted therapies for AML as a representation of possible agents for precision medicine. We will discuss experimental and preclinical data for FLT3, IDH1, BCL-2, Hedgehog pathway inhibitors, and epitherapy
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
New approaches to idiopathic neutropenia in the era of clonal hematopoiesis
Full text linkIsolated chronic idiopathic neutropenia (CIN) is a rare disease with multiple contributing etiologies that must be ruled
out before establishing a diagnosis. We studied clinical and molecular data of 238 consecutive adult patients with CIN.
Autoimmune neutropenia was present in 28% of our cohort. In contrast, T cell-mediated neutropenia was the main
underlying pathological mechanism among patients with T cell expansions, such as T-cell large granular lymphocytic
leukemia (T-LGL) and T cell clonopathy of undetermined signifcance, found in 37% and 8% of cases, respectively.
Patients with neutropenia also had hypogammaglobulinemia (6%) and/or monoclonal gammopathy of undetermined signifcance (5%). NGS application has further broadened the spectrum of causes of CIN by including manifestations of clonal hematopoiesis, present in 12% of cases. TET2 (3%), TP53 (2%), and IDH1/IDH2 (2%) mutations were
the most commonly found and were enriched in cases with T-LGL. We show that these clinico-molecular associations
can be simultaneously present, complicating a proper diagnostic distinction within the broader entity of seemingly
idiopathic neutropenia of autoimmune origin. Identifcation of etiologic culprits may also guide rational selection of
therapies
Increased expression of the signaling lymphocyte-activation molecule (mSLAM) in patients with paroxysmal nocturnal hemoglobinuria (PNH).
No full textRisk and Prognostic Factors of Extra-Nodal Hodgkin Lymphoma: Single Jordanian Center Experience.
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