NF-κB signaling pathway as target for antiplatelet activity
In different nucleated cells, NF-κB has long been considered a prototypical proinflammatory signaling pathway with the expression of proinflammatory genes.Although platelets lack a nucleus, a number of functional transcription factors are involved in activated platelets, such as NF-κB. In platelet activation NF-κB regulation events include IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation. Multiple pathways contribute to platelet activation and NF-κB is a common pathway in this activation. (Source: Blood Reviews)
Source: Blood Reviews - March 15, 2016 Category: Hematology Authors: Eduardo Fuentes, Armando Rojas, Iván Palomo Tags: Review Source Type: research
Specific removal of alloreactive T-cells to prevent GvHD in hemopoietic stem cell transplantation: rationale, strategies and perspectives
Hemopoietic stem cell transplantation (HSCT) is a standard procedure for treatment of malignant and non-malignant hematological diseases. HSCT donors include HLA-identical siblings, matched or mismatched unrelated donors and haploidentical related donors. Graft-versus-host disease (GvHD), mediated by donor alloreactive T-cells in the graft, can be triggered by minor histocompatibility antigens in HLA-identical pairs, by alleles at loci not considered for MUD-matching or by the mismatched haplotype in haplo-HSCT. (Source: Blood Reviews)
Source: Blood Reviews - March 14, 2016 Category: Hematology Authors: Giuseppina Li Pira, Stefano Di Cecca, Mauro Montanari, Lorenzo Moretta, Fabrizio Manca Tags: REVIEW Source Type: research
NF- κB signaling pathway as target for antiplatelet activity
In different nucleated cells, NF- κB has long been considered a prototypical proinflammatory signaling pathway with the expression of proinflammatory genes.Although platelets lack a nucleus, a number of functional transcription factors are involved in activated platelets, such as NF-κB. In platelet activation NF-κB regulation eve nts include IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation. Multiple pathways contribute to platelet activation and NF-κB is a common pathway in this activation. (Source: Blood Reviews)
Source: Blood Reviews - March 14, 2016 Category: Hematology Authors: Eduardo Fuentes, Armando Rojas, Iv án Palomo Tags: REVIEW Source Type: research
Epigenetics: A primer for clinicians
With recent advances in cellular biology, we now appreciate that modifications to DNA and histones can have a profound impact on transcription and function, even in the absence of changes to DNA sequence. These modifications, now commonly referred to as “epigenetic” alterations, have changed how we understand cell behavior, reprogramming and differentiation and have provided significant insight into the mechanisms underlying carcinogenesis. Epigenetic alterations, to this point, are largely identified by changes in DNA methylation and hydroxymethylation as well as methylation, acetylation, and phosphorylation of histon...
Source: Blood Reviews - February 24, 2016 Category: Hematology Authors: Benjamin E. Paluch, Abdul R. Naqash, Zachary Brumberger, Michael J. Nemeth, Elizabeth A. Griffiths Tags: Review Source Type: research
Epigenetics: A primer for clinicians
With recent advances in cellular biology, we now appreciate that modifications to DNA and histones can have a profound impact on transcription and function, even in the absence of changes to DNA sequence. These modifications, now commonly referred to as “epigenetic” alterations, have changed how we understand cell behavior, reprogramming and differentiation and have provided significant insight into the mechanisms underlying carcinogenesis. Epigenetic alterations, to this point, are largely identified by changes in DNA methylation and hydroxyme thylation as well as methylation, acetylation, and phosphorylation of histo...
Source: Blood Reviews - February 23, 2016 Category: Hematology Authors: Benjamin E. Paluch, Abdul R. Naqash, Zachary Brumberger, Michael J. Nemeth, Elizabeth A. Griffiths Tags: Review Source Type: research
Update on rational targeted therapy in AML
Acute myeloid leukemia (AML) remains a challenge to both patients and clinicians. Despite improvements in our understanding of the disease, treatment has changed minimally and outcomes remain poor for the majority of patients. Within the last decade, there have been an increasing number of potential targets and pathways identified for development in AML. The classes of agents described in this review include but are not limited to epigenetic modifiers such as IDH inhibitors, BET inhibitors and HDAC inhibitors as well as cell cycle and signaling inhibitors such as Aurora kinase inhibitors and CDK inhibitors. (Source: Blood Reviews)
Source: Blood Reviews - February 21, 2016 Category: Hematology Authors: Danielle Shafer, Steven Grant Tags: REVIEW Source Type: research
Update on rational targeted therapy in AML
Acute myeloid leukemia (AML) remains a challenge to both patients and clinicians. Despite improvements in our understanding of the disease, treatment has changed minimally and outcomes remain poor for the majority of patients. Within the last decade, there have been an increasing number of potential targets and pathways identified for development in AML. The classes of agents described in this review include but are not limited to epigenetic modifiers such as IDH inhibitors, BET inhibitors, and HDAC inhibitors as well as cell cycle and signaling inhibitors such as Aurora kinase inhibitors and CDK inhibitors. (Source: Blood Reviews)
Source: Blood Reviews - February 20, 2016 Category: Hematology Authors: Danielle Shafer, Steven Grant Tags: REVIEW Source Type: research
Erythrocytes and their role as health indicator: using structure in a patient-orientated precision medicine approach
The relevance of erythrocyte light microscopy analysis (a well-known haematological method) is under the spotlight, however there is a place for innovative electron microscopy, (together with biochemical markers) in a pathology laboratory. Inflammation is a key indicator of the health status and erythrocytes are extremely sensitive to oxidative stress or cytokine upregulation, which typically accompany systemic inflammation in most diseases. They are probably the most adaptable cells, and due to their short lifespan, may form a vital indicator of health, and could play a central part in tracking disease and treatment. (Source: Blood Reviews)
Source: Blood Reviews - February 2, 2016 Category: Hematology Authors: Etheresia Pretorius, Oore-ofe O. Olumuyiwa-Akeredolu, Sthembile Mbotwe, Janette Bester Tags: REVIEW Source Type: research
Erythrocytes and their role as health indicator: Using structure in a patient-orientated precision medicine approach
The relevance of erythrocyte light microscopy analysis (a well-known haematological method) is under the spotlight, however there is a place for innovative electron microscopy, (together with biochemical markers) in a pathology laboratory. Inflammation is a key indicator of the health status and erythrocytes are extremely sensitive to oxidative stress or cytokine upregulation, which typically accompany systemic inflammation in most diseases. They are probably the most adaptable cells, and due to their short lifespan, may form a vital indicator of health, and could play a central part in tracking disease and treatment. (Source: Blood Reviews)
Source: Blood Reviews - February 1, 2016 Category: Hematology Authors: Etheresia Pretorius, Oore-ofe O. Olumuyiwa-Akeredolu, Sthembile Mbotwe, Janette Bester Tags: REVIEW Source Type: research
DAMP and DIC: The role of extracellular DNA and DNA-binding proteins in the pathogenesis of DIC
Disseminated intravascular coagulation (DIC) is a heterogeneous group of disorders, which manifest as a spectrum of haemorrhage and thrombosis complicating many primary conditions including sepsis, trauma and malignancies. The pathophysiology of this condition is complex. In the recent years there is growing evidence that damage associated molecular patterns (DAMPs) play a crucial role in the pathogenesis of DIC. Upon cell-death and/or cell activation of hematopoietic and parenchymal cells extracellular cell-free DNA as well as DNA binding proteins (e.g. (Source: Blood Reviews)
Source: Blood Reviews - December 30, 2015 Category: Hematology Authors: Patricia Liaw, Takashi Ito, Toshiaki Iba, Jecko Thachil, Sacha Zeerleder Tags: REVIEW Source Type: research
Coagulation abnormalities of sickle cell disease: Relationship with clinical outcomes and the effect of disease modifying therapies
Sickle cell disease (SCD) is a hypercoagulable state. Patients exhibit increased platelet activation, high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the non-crisis “steady state.” Furthermore, SCD is characterized by an increased risk of thrombotic complications. The pathogenesis of coagulation activation in SCD appears to be multi-factorial, with contributions from ischemia–reperfusion injury and inflammation, hemolysis and nitric oxide deficiency, and increased sickle R...
Source: Blood Reviews - December 24, 2015 Category: Hematology Authors: Denis Noubouossie, Nigel S. Key, Kenneth I. Ataga Tags: REVIEW Source Type: research
Targeted therapies for CLL: Practical issues with the changing treatment paradigm
Chemoimmunotherapy (CIT) such as FCR (fludarabine, cyclophosphamide, rituximab) has been the standard first-line therapy for younger patients with CLL. In the last few years, several novel targeted therapies have been developed for patients with CLL. These include B-cell receptor (BCR) inhibitors such as Bruton tyrosine kinase (BTK) inhibitors, PI3 kinase inhibitors, and Syk inhibitors, novel anti-CD20 monoclonal antibodies such as ofatumumab and obinutuzumab, and Bcl-2 antagonists such as venetoclax (ABT-199). (Source: Blood Reviews)
Source: Blood Reviews - December 23, 2015 Category: Hematology Authors: Nitin Jain, Susan O'Brien Tags: REVIEW Source Type: research
