Rationale for assessing the therapeutic potential of resveratrol in hematological malignancies
Promising results from pre-clinical studies on the naturally-occurring polyphenol resveratrol have generated considerable interest and somewhat excessive expectations regarding the therapeutic potential of this compound for treating or preventing various diseases, including cardiovascular and neurodegenerative disorders and cancer. Resveratrol has potent inhibitory activity in vitro against various tumor types, including cell lines derived from virtually all blood malignancies. Pharmacological studies have shown that resveratrol is safe for humans but has poor bioavailability, due to its extensive hepatic metabolism. (Source: Blood Reviews)
Source: Blood Reviews - July 4, 2018 Category: Hematology Authors: J. Luis Espinoza, Yu Kurokawa, Akiyoshi Takami Tags: Review Source Type: research
Are low-molecular-weight heparins safe and effective in children? A systematic review
The incidence of venous thromboembolism (VTE) in children is rising. Hence, there is an increasing off-label use of low-molecular-weight heparin (LMWH). There is little data about therapeutic and prophylactic LWMH dosages, and their safety and efficacy. This systematic review provided an oversight of the therapeutic and prophylactic dosages of LMWH required to reach therapeutic and prophylactic target ranges. Furthermore, the safety and efficacy of LMWH, in terms of bleeding complications, achieving therapeutic and prophylactic anti-factor Xa levels, development of (recurrent) VTE and cloth resolution were reviewed. (Source: Blood Reviews)
Source: Blood Reviews - June 27, 2018 Category: Hematology Authors: Irene L.M. Klaassen, Jeanine J. Sol, Monique H. Suijker, K. Fijnvandraat, Marianne D. van de Wetering, C. Heleen van Ommen Tags: Review Source Type: research
Venous thromboembolism incidence in hematologic malignancies
Venous thromboembolism (VTE) remains a major cause of morbidity and mortality in patients with cancer. Although some very well validated scores delineate the risk of VTE by cancer subtype and other risk factors, hematologic malignancies are underrepresented in these models. This subgroup represents a unique entity that undergoes therapy that can be thrombogenic. The overall risk of VTE in patients with leukemia depends on the use of L-asparaginase treatment, older age, comorbidities and central venous catheters. (Source: Blood Reviews)
Source: Blood Reviews - June 20, 2018 Category: Hematology Authors: Natasha Kekre, Jean M. Connors Tags: Review Source Type: research
Modelling human haemoglobin switching
Genetic lesions of the β-globin gene result in haemoglobinopathies such as β-thalassemia and sickle cell disease. To discover and test new molecular medicines for β-haemoglobinopathies, cell-based and animal models are now being widely utilised. However, multiple in vitro and in vivo models are required due to the comp lex structure and regulatory mechanisms of the human globin gene locus, subtle species-specific differences in blood cell development, and the influence of epigenetic factors. Advances in genome sequencing, gene editing, and precision medicine have enabled the first generation of molecular therapies aimed...
Source: Blood Reviews - June 15, 2018 Category: Hematology Authors: Sarah T. Diepstraten, Adam H. Hartb Tags: Review Source Type: research
Increased bone resorption in hemophilia
In patients with hemophilia, osteoporosis is frequently observed for which the etiology remains unclear. The aim of this paper is to review the available experimental evidence indicating the presence of this disorder in patients with hemophilia, explore the potential mechanisms which may lead to reduced bone mineral density (BMD) and speculate on useful interventions to circumvent it. A narrative review of the English literature up to April 2018 was performed. The available evidence demonstrates an increased rate of bone resorption and an excess of osteoporosis among patients with hemophilia. (Source: Blood Reviews)
Source: Blood Reviews - May 25, 2018 Category: Hematology Authors: E. Carlos Rodriguez-Merchan, Leonard A. Valentino Tags: Review Source Type: research
The evolving understanding of factor VIII binding sites and implications for the treatment of hemophilia A
Hemophilia A is caused by decreased or dysfunctional blood coagulation factor VIII (FVIII). Recent developments in the understanding of FVIII biology, in particular the nature of FVIII binding sites on platelets, may provide new insight into the limitations of current assays. Recent data suggest that the phospholipid vesicles, which represent nonphysiologic membranes of high phosphatidylserine (PS) content, poorly reflect functional FVIII binding sites critical to coagulation. This narrative review describes the function of FVIII in clotting and discusses our evolving understanding of FVIII binding sites and their clinical...
Source: Blood Reviews - May 23, 2018 Category: Hematology Authors: Gary E. Gilbert Tags: Review Source Type: research
Current status and trends in the diagnostics of AML and MDS
Diagnostics of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) have recently been experiencing extensive modifications as regards the incorporation of next-generation sequencing (NGS) strategies into established diagnostic algorithms, classification and risk stratification systems, and minimal residual disease (MRD) detection. Considering the increasing arsenal of targeted therapies (e.g. FLT3 or IDH1/IDH2 inhibitors) for AML, timely and comprehensive molecular mutation screening has arrived in daily practice. (Source: Blood Reviews)
Source: Blood Reviews - April 26, 2018 Category: Hematology Authors: Evgenii Shumilov, Johanna Flach, Alexander Kohlmann, Yara Banz, Nicolas Bonadies, Martin Fiedler, Thomas Pabst, Ulrike Bacher Tags: Review Source Type: research
Infections in patients with chronic lymphocytic leukaemia: Mitigating risk in the era of targeted therapies
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection. (Source: Blood Reviews)
Source: Blood Reviews - April 23, 2018 Category: Hematology Authors: Benjamin W. Teh, Constantine S. Tam, Sasanka Handunnetti, Leon J. Worth, Monica A. Slavin Tags: Review Source Type: research
Myeloid-derived suppressor cells in lymphoma: The good, the bad and the ugly
Lymphomas cause significant morbidity and mortality worldwide. A substantial number of patients ultimately relapse after standard treatment. However, the efficacy of these therapies can be counteracted by the patients' immune system, more specifically by myeloid-derived suppressor cells (MDSC). MDSC are a heterogeneous group of immature myeloid cells that suppress the innate and adaptive immune system via different mechanisms and accumulate under pathological conditions, such as cancer. MDSC play a role in the induction and progression of cancer and immune evasion. (Source: Blood Reviews)
Source: Blood Reviews - April 18, 2018 Category: Hematology Authors: A. Betsch, O. Rutgeerts, S. Fevery, B. Sprangers, G. Verhoef, D. Dierickx, M. Beckers Tags: Review Source Type: research
Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies, an in-depth review
Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRP α triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibod y molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. (Source: Blood Reviews)
Source: Blood Reviews - April 13, 2018 Category: Hematology Authors: Atlantis Russ, Anh B. Hua, William R. Montfort, Bushra Rahman, Irbaz Bin Riaz, Muhammad Umar Khalid, Jennifer S. Carew, Steffan T. Nawrocki, Daniel Persky, Faiz Anwer Tags: Review Source Type: research
Iron toxicity – Its effect on the bone marrow
Excess iron can be extremely toxic for the body and may cause organ damage in the absence of iron chelation therapy. Preclinical studies on the role of free iron on bone marrow function have shown that iron toxicity leads to the accumulation of reactive oxygen species, affects the expression of genes coding for proteins that regulate hematopoiesis, and disrupts hematopoiesis. These effects could be partially attenuated by iron-chelation treatment with deferasirox, suggesting iron toxicity may have a negative impact on the hematopoietic microenvironment. (Source: Blood Reviews)
Source: Blood Reviews - April 13, 2018 Category: Hematology Authors: Alessandro Isidori, Lorenza Borin, Elena Elli, Roberto Latagliata, Bruno Martino, Giuseppe Palumbo, Federica Pilo, Federica Loscocco, Giuseppe Visani, Paolo Cianciulli Tags: Review Source Type: research
Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies, an in-depth review
Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRP α triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibod y molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. (Source: Blood Reviews)
Source: Blood Reviews - April 13, 2018 Category: Hematology Authors: Atlantis Russ, Anh B. Hua, William R. Montfort, Bushra Rahman, Irbaz Bin Riaz, Muhammad Umar Khalid, Jennifer S. Carew, Steffan T. Nawrocki, Daniel Persky, Faiz Anwer Tags: Review Source Type: research
Iron toxicity – Its effect on the bone marrow
Excess iron can be extremely toxic for the body and may cause organ damage in the absence of iron chelation therapy. Preclinical studies on the role of free iron on bone marrow function have shown that iron toxicity leads to the accumulation of reactive oxygen species, affects the expression of genes coding for proteins that regulate hematopoiesis, and disrupts hematopoiesis. These effects could be partially attenuated by iron-chelation treatment with deferasirox, suggesting iron toxicity may have a negative impact on the hematopoietic microenvironment. (Source: Blood Reviews)
Source: Blood Reviews - April 13, 2018 Category: Hematology Authors: Alessandro Isidori, Lorenza Borin, Elena Elli, Roberto Latagliata, Bruno Martino, Giuseppe Palumbo, Federica Pilo, Federica Loscocco, Giuseppe Visani, Paolo Cianciulli Tags: Review Source Type: research
