A storm in the niche: Iron, oxidative stress and haemopoiesis
Iron, although essential, is harmful in high amounts. Oxidative stress as a result of excess reactive oxygen species (ROS) and a prooxidative/antioxidative imbalance between ROS production and elimination, play a key role in cellular damage. There is evidence to support the role of ROS in the pathogenesis of a range of diseases including the myelodysplastic syndromes (MDS) and leukaemia. Oxidative stress seems to affect the self-renewal, proliferation and differentiation of haematopoietic stem cells and impair cell growth. (Source: Blood Reviews)
Source: Blood Reviews - August 11, 2017 Category: Hematology Authors: Federica Pilo, Emanuele Angelucci Tags: Review Source Type: research
Apoptosis signaling and BCL-2 pathways provide opportunities for novel targeted therapeutic strategies in hematologic malignances
Apoptosis is an essential biological process involved in tissue homeostasis and immunity. Aberrations of the two main apoptotic pathways, extrinsic and intrinsic, have been identified in hematological malignancies; many of these aberrations are associated with pathogenesis, prognosis and resistance to standard chemotherapeutic agents. Targeting components of the apoptotic pathways, especially the chief regulatory BCL-2 family in the intrinsic pathway, has proved to be a promising therapeutic approach for patients with hematological malignances, with the expectation of enhanced efficacy and reduced adverse events. (Source: Blood Reviews)
Source: Blood Reviews - August 7, 2017 Category: Hematology Authors: Huanling Wu, L. Jeffrey Medeiros, Ken H. Young Tags: Review Source Type: research
Pathways towards indolent B-cell lymphoma — Etiology and therapeutic strategies
Although patients with indolent B-cell lymphomas have a relatively good survival rate, conventional chemotherapy is not curative. Disease courses are typically characterized by multiple relapses and progressively shorter response duration with subsequent lines of therapy. There has been an explosion of innovative targeted agents in the past years. This review discusses current knowledge on the etiology of indolent B-cell lymphomas with respect to the role of micro-organisms, auto-immune diseases, and deregulated pathways caused by mutations. (Source: Blood Reviews)
Source: Blood Reviews - August 5, 2017 Category: Hematology Authors: Michiel van den Brand, Blanca Scheijen, Corine J. Hess, J. Han JM van Krieken, Patricia J.T.A. Groenen Tags: Review Source Type: research
The role of endothelium in the onset of antibody-mediated TRALI
Transfusion Related Acute Lung Injury (TRALI) is one of the leading causes of mortality and morbidity following blood transfusion. The mechanisms behind the disease are not yet fully understood but seem to involve many different activating pathways and donor factors, in synergy with patient susceptibility. Studies have focused mostly on neutrophil activation, as aggregates of neutrophils and edema in lungs are found in post-mortem histological sections. This review aims to highlight the role of the endothelium in TRALI, as activated endothelium is the main promoter of leukocyte transmigration, and creates the barrier betwe...
Source: Blood Reviews - August 4, 2017 Category: Hematology Authors: K.S.H. Morsing, A.L. Peters, J. van Buul, A.P.J. Vlaar Tags: Review Source Type: research
Treatment of acute myeloid leukemia in the next decade – Towards real-time functional testing and personalized medicine
Information arising from next generation sequencing of leukemia genome has shed important light on the heterogeneous and combinatorial driver events in acute myeloid leukemia (AML). It has also provided insight as to its intricate signaling pathways operative in the disease pathogenesis. These have also become biomarkers and targets for therapeutic intervention. Emerging evidence from in vitro drug screening has demonstrated its potential value in predicting clinical drug responses in specific AML subtypes. (Source: Blood Reviews)
Source: Blood Reviews - August 4, 2017 Category: Hematology Authors: Stephen Sze-Yuen Lam, Alex Bai-Liang He, Anskar Yu-Hung Leung Tags: Review Source Type: research
Diagnosis and management of the antiphospholipid syndrome
Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy complications in the presence of persistent antiphospholipid antibodies (APLA). Laboratory diagnosis of APLA depends upon the detection of a lupus anticoagulant, which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin (aCL) and anti- β2-glycoprotein-1 (β2GPI) antibodies. APLA are primarily directed toward phospholipid binding proteins. Pathophysiologic mechanisms underlying thrombosis and pregnancy loss in APS include APLA induced cellular activation, inhibition of natural anticoagulant and fibrinolytic systems, an...
Source: Blood Reviews - July 30, 2017 Category: Hematology Authors: Shruti Chaturvedi, Keith R. McCrae Tags: Review Source Type: research
Therapeutic use of transferrin to modulate anemia and conditions of iron toxicity
As the main iron transporter, transferrin delivers iron to target tissues like the bone marrow for erythropoiesis. Also, by binding free iron, transferrin prevents formation of reactive oxygen species. Transferrin deficiency due to congenital hypotransferrinemia is characterized by anemia as well as oxidative stress related to toxic free iron. Transferrin supplementation may be beneficial in two ways. First, transferrin can correct anemia by modulating the amount of iron that is available for erythropoiesis. (Source: Blood Reviews)
Source: Blood Reviews - July 24, 2017 Category: Hematology Authors: M. Boshuizen, K. van der Ploeg, L. von Bonsdorff, B.J. Biemond, S.S. Zeerleder, R. van Bruggen, N.P. Juffermans Tags: Review Source Type: research
Platelet populations and priming in hematological diseases
In healthy subjects and patients with hematological diseases, platelet populations can be distinguished with different response spectra in hemostatic and vascular processes. These populations appear to partly overlap, and are less distinct than those of leukocytes. The heterogeneity is linked to structural properties, and is enforced by inequalities in the environment. Contributing factors are variability between megakaryocytes, platelet ageing, and positive or negative priming of platelets during their time in circulation. (Source: Blood Reviews)
Source: Blood Reviews - July 22, 2017 Category: Hematology Authors: Constance C.F.M.J. Baaten, Hugo ten Cate, Paola E.J. van der Meijden, Johan W.M. Heemskerk Tags: Review Source Type: research
The who, how and why: Allogeneic transplant for acute myeloid leukemia in patients older than 60years
Acute myelogenous leukemia (AML) is primarily a disease of the elderly, and as such, our approach to treatment needs to be tailored to address an aging population. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative treatment for intermediate and high risk AML, and until recently, its use had been limited to a younger population and dependent on availability of a donor. Advances in conditioning regimens, supportive care, and the use of alternative donor sources have greatly expanded access to this therapy. (Source: Blood Reviews)
Source: Blood Reviews - July 15, 2017 Category: Hematology Authors: Sarah A. Wall, Steven Devine, Sumithira Vasu Tags: Review Source Type: research
The skin as a window to the blood: Cutaneous manifestations of myeloid malignancies
Cutaneous manifestations of myeloid malignancies are common and have a broad range of presentations. These skin findings are classified as specific, due to direct infiltration by malignant hematopoietic cells, or non-specific. Early recognition and diagnosis can have significant clinical implications, as skin manifestations may be the first indication of underlying hematologic malignancy, can reflect the immune status and stage of disease, and cutaneous reactions may occur from conventional and targeted agents used to treat myeloid disease. (Source: Blood Reviews)
Source: Blood Reviews - July 14, 2017 Category: Hematology Authors: Alvin W. Li, Emily S. Yin, Maximilian Stahl, Tae Kon Kim, Gauri Panse, Amer M. Zeidan, Jonathan S. Leventhal Tags: Review Source Type: research
Catalyzing improvements in ALL therapy with asparaginase
Asparaginase remains a cornerstone of ALL therapy and is one of the key contributing factors to improved outcomes in adolescent and young adult (AYA) patients treated on pediatric protocols. Asparagine depletion has been associated with improved outcomes in ALL patients; this has led to an increased emphasis on optimizing asparagine depletion in ALL patients of all ages. To ensure adequate asparagine depletion, the use of therapeutic drug monitoring of asparaginase therapy holds much promise, yet remains underutilized in practice. (Source: Blood Reviews)
Source: Blood Reviews - July 5, 2017 Category: Hematology Authors: Bernard L. Marini, Anthony J. Perissinotti, Dale L. Bixby, Julia Brown, Patrick W. Burke Tags: Review Source Type: research
To serve and protect: The modulatory role of von Willebrand factor on factor VIII immunogenicity
Hemophilia A is a bleeding disorder characterized by the absence or dysfunction of blood coagulation factor VIII (FVIII). Patients are treated with regular infusions of FVIII concentrate. In response to treatment, approximately 30% of patients with severe hemophilia A develop inhibitory antibodies targeting FVIII. Both patient and treatment related risk factors for inhibitor development have been described. Multiple studies comparing the immunogenicity of recombinant and plasma-derived FVIII have yielded conflicting results. (Source: Blood Reviews)
Source: Blood Reviews - July 4, 2017 Category: Hematology Authors: Robin Hartholt, Alice S. van Velzen, Ivan Peyron, Anja ten Brinke, Karin FijnvanDraat, Jan Voorberg Tags: Review Source Type: research
Eryptosis in health and disease: A paradigm shift towards understanding the (patho)physiological implications of programmed cell death of erythrocytes
During the course of their natural ageing and upon injury, anucleate erythrocytes can undergo an unconventional apoptosis-like cell death, termed eryptosis. Eryptotic erythrocytes display a plethora of morphological alterations including volume reduction, membrane blebbing and breakdown of the membrane phospholipid asymmetry resulting in phosphatidylserine externalization which, in turn, mediates their phagocytic recognition and clearance from the circulation. Overall, the eryptosis machinery is tightly orchestrated by a wide array of endogenous mediators, ion channels, membrane receptors, and a host of intracellular signa...
Source: Blood Reviews - June 17, 2017 Category: Hematology Authors: Syed M. Qadri, Rosi Bissinger, Ziad Solh, Per-Arne Oldenborg Tags: Review Source Type: research
Interleukin-1 β as emerging therapeutic target in hematological malignancies and potentially in their complications
Interleukin-1 β (IL-1β) is a pleiotropic cytokine that exerts multiple roles in both physiological and pathological conditions. It is produced by different cell subsets, and drives a wide range of inflammatory responses in numerous target cells. Enhanced IL-1β signaling is a common event in patients of hematol ogical malignancies. Recent body of evidence obtained in preclinical models shows the pathogenic role of these alterations, and the promising therapeutic value of IL-1 targeting. In this review, we further highlight a potential contribution of IL-1β linking to complications and autoimmune disease t hat should be ...
Source: Blood Reviews - May 3, 2017 Category: Hematology Authors: Lorena Arranz, Maria del Mar Arriero, Alicia Villatoro Tags: Review Source Type: research
Dancing partners at the ball: Rational selection of next generation anti-CD20 antibodies for combination therapy of chronic lymphocytic leukemia in the novel agents era
The anti-CD20 antibodies represent a major advancement in the therapeutic options available for chronic lymphocytic leukemia. The addition of rituximab, ofatumumab and obinutuzumab to various chemotherapy regimens has led to considerable improvements in both response and survival. Ocaratuzumab, veltuzumab and ublituximab are currently being explored within the trial setting. We review the current status of these antibodies, and discuss how their mechanisms of action may impact on the choice of combinations with novel small molecule agents. (Source: Blood Reviews)
Source: Blood Reviews - May 3, 2017 Category: Hematology Authors: L.A. Butler, C.S. Tam, J.F. Seymour Tags: Review Source Type: research
