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Blood Reviews

Alessandro Morotti, Stefania Rocca, Giovanna Carrà, Giuseppe Saglio, Mara Brancaccio
Myeloproliferative neoplasms (MPNs) are defined according to the 2008 World Health Organization (WHO) classification and the recent 2016 revision. Over the years, several genetic lesions have been associated with the development of MPNs, with important consequences for identifying unique biomarkers associated with specific neoplasms and for developing targeted therapies. Defining the genotype-phenotype relationship in MPNs is essential to identify driver somatic mutations that promote MPN development and maintenance in order to develop curative targeted therapies...
November 24, 2016: Blood Reviews
Jacob Grinfeld, Anna L Godfrey
The JAK2V617F mutation accounts for the vast majority of patients with polycythaemia vera (PV) and around half of those with other Philadelphia-negative myeloproliferative neoplasms. Since its discovery in 2005, numerous insights have been gained into the pathways by which JAK2V617F causes myeloproliferation, including activation of JAK-STAT signalling but also through other canonical and non-canonical pathways. A variety of mechanisms explain how this one mutation can be associated with distinct clinical disorders, demonstrating how constitutional and acquired factors may interact in the presence of a single mutation to determine disease phenotype...
November 15, 2016: Blood Reviews
Li Yu, Ling Li, L Jeffrey Medeiros, Ken H Young
The NF-κB pathway, a critical regulator of apoptosis, plays a key role in many normal cellular functions. Genetic alterations and other mechanisms leading to constitutive activation of the NF-κB pathway contribute to cancer development, progression and therapy resistance by activation of downstream anti-apoptotic pathways, unfavorable microenvironment interactions, and gene dysregulation. Not surprisingly, given its importance to normal and cancer cell function, the NF-κB pathway has emerged as a target for therapy...
October 13, 2016: Blood Reviews
Nicholas E Mamrak, Akiko Shimamura, Niall G Howlett
Fanconi anemia (FA) is a rare autosomal and X-linked genetic disease characterized by congenital abnormalities, progressive bone marrow failure (BMF), and increased cancer risk during early adulthood. The median lifespan for FA patients is approximately 33years. The proteins encoded by the FA genes function together in the FA-BRCA pathway to repair DNA damage and to maintain genome stability. Within the past two years, five new FA genes have been identified-RAD51/FANCR, BRCA1/FANCS, UBE2T/FANCT, XRCC2/FANCU, and REV7/FANCV-bringing the total number of disease-causing genes to 21...
October 13, 2016: Blood Reviews
Nikolai A Podoltsev, Maximilian Stahl, Amer M Zeidan, Steven D Gore
More than half of the patients with acute myeloid leukaemia (AML) are older than 60years. The treatment outcomes in this group remain poor with a median overall survival of <1year. Selecting initial treatment for these patients involves an assessment of 'fitness' for induction chemotherapy. This is done based on patient and disease-related characteristics which help to estimate treatment-related mortality and chance of complete remission with induction chemotherapy. If the risk of treatment-related mortality is high and/or the likelihood of a patient achieving a complete remission is low, lower-intensity treatment (low-dose cytarabine, decitabine and azacitidine) should be discussed...
October 8, 2016: Blood Reviews
Xueyan Chen, Brent L Wood
Minimal residual disease (MRD) after therapy has unequivocal prognostic value in acute leukemia. Over the past 20years, a number of techniques have evolved into routine laboratory tools to detect MRD, most notably, multiparametric flow cytometry (MFC) and quantitative polymerase chain reaction (PCR)-based molecular methods. There is growing evidence that the presence of MRD detected by MFC or molecular methods provides independent prognostic information and is associated with an increased risk of relapse and shortened survival...
October 5, 2016: Blood Reviews
Allison Rosenthal, Anas Younes
Diffuse large B-cell lymphomas with aberrations in MYC, BCL2 and/or BCL6 by genetic alterations or protein expression represent a group of high grade B-cell lymphomas with inferior outcomes when treated with standard RCHOP chemotherapy. As a result, intensified induction regimens have been suggested in an effort to improve outcomes. Conclusions to date have largely been drawn from retrospective data although prospective data is slowly starting to emerge. Chemoimmunotherapy refractoriness is problematic and relapse rates are high...
September 30, 2016: Blood Reviews
L M Van der Pol, A T A Mairuhu, C Tromeur, F Couturaud, M V Huisman, F A Klok
Because pregnant women have an increased risk of venous thromboembolism (VTE) and at the same time normal pregnancy is associated with symptoms, mimicking those present in the setting of acute pulmonary embolism (PE), the latter diagnosis is frequently suspected in this patient category. Since imaging tests expose both mother and foetus to ionizing radiation, the ability to rule out PE based on non-radiological diagnostic tests is of paramount importance. However, clinical decision rules have only been scarcely evaluated in the pregnant population with suspected PE, while D-dimer levels lose diagnostic accuracy due to a physiological increase during normal pregnancy...
September 29, 2016: Blood Reviews
Livio Pagano, Alessandro Busca, Anna Candoni, Chiara Cattaneo, Simone Cesaro, Rosa Fanci, Gianpaolo Nadali, Leonardo Potenza, Domenico Russo, Mario Tumbarello, Annamaria Nosari, Franco Aversa
Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in immunocompromised patients. Patients with hematological malignancies undergoing conventional chemotherapy, autologous or allogeneic hematopoietic stem cell transplantation are considered at high risk, and Aspergillus spp. represents the most frequently isolated micro-organisms. In the last years, attention has also been focused on other rare molds (e.g., Zygomycetes, Fusarium spp.) responsible for devastating clinical manifestations...
September 17, 2016: Blood Reviews
Yishai Ofran, Shai Izraeli
Recent comprehensive genetic studies revealed numerous genetic aberrations underlying a group of high-risk leukemias that share a specific activated kinase gene expression pattern. These ALLs were first recognized by the expression profile similar to that of Philadelphia chromosome-positive ALL and currently can be sub-classified by the main aberrantly activated kinase in the leukemic cells. We herein review the biological mechanisms and diagnostic and clinical challenges presented by these leukemias.
September 16, 2016: Blood Reviews
Geoffrey S Kannan, Arianexys Aquino-Lopez, Dean A Lee
Natural killer cells were first described over 40years ago, but the last 15years has shown tremendous progress in our understanding of their biology and our ability to manipulate them for clinical therapeutic effect. Despite the increased understanding by clinicians and scientists investigating these cells, their biology remains a confusing subject for many because of the wide array of receptors, complex interactions, multiple models of predicting function, and contradictory data in the literature. While they are microscopically indistinguishable from T cells and share many of the same effector functions, their mechanisms of target recognition are completely distinct from yet complimentary to T cells...
September 9, 2016: Blood Reviews
Jeanette Prada-Arismendy, Johanna C Arroyave, Sarah Röthlisberger
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The pathophysiology of this disease is just beginning to be understood at the cellular and molecular level, and currently cytogenetic markers are the most important for risk stratification and treatment of AML patients. However, with the advent of new technologies, the detection of other molecular markers such as point mutations and characterization of epigenetic and proteomic profiles, have begun to play an important role in how the disease is approached...
September 2, 2016: Blood Reviews
Bethany T Samuelson, Adam Cuker
Direct oral anticoagulants (DOACs) offer noninferior efficacy and improved safety compared to vitamin K antagonists (VKAs) for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Unlike VKAs, DOACs do not require routine laboratory monitoring of anticoagulant effect and dose adjustment. In certain situations, however, laboratory assessment of anticoagulant effect may be desirable. Here we review the utility of currently available assays for assessment of DOAC effect and recommend an optimal assessment strategy for each drug, including calibrated dilute thrombin time or ecarin-based assays for dabigatran and calibrated anti-Xa activity assays for the factor Xa inhibitors...
September 2, 2016: Blood Reviews
Alaa M Ali, Farrokh Dehdashti, John F DiPersio, Amanda F Cashen
No abstract text is available yet for this article.
September 2016: Blood Reviews
E Carlos Rodriguez-Merchan
No abstract text is available yet for this article.
September 2016: Blood Reviews
Aziz Nazha, Thomas Prebet, Steven Gore, Amer M Zeidan
Chronic myelomonocytic leukemia (CMML) is a unique disease entity with overlap components of both myelodysplastic syndrome and myeloproliferative neoplasms. CMML is a clonal hematopoietic stem cell neoplasm characterized by monocytosis, cytopenias, and extramedullary manifestations such as splenomegaly. The disease is rare and has undergone revisions in its classification. We review the recent classification strategies as well as diagnostic criteria, focusing on the new insights into the genetic alterations and unique pathophysiology of the disease...
September 2016: Blood Reviews
Kuldeepsinh Rana, Keith B Neeves
Blood flow regulates coagulation and fibrin formation by controlling the transport, or mass transfer, of zymogens, co-factors, enzymes, and inhibitors to, from, and within a growing thrombus. The rate of mass transfer of these solutes relative to their consumption or production by coagulation reactions determines, in part, the rate of thrombin generation, fibrin deposition, and thrombi growth. Experimental studies on the influence of blood flow on specific coagulation reactions are reviewed here, along with a theoretical framework that predicts how flow influences surface-bound coagulation binding and enzymatic reactions...
September 2016: Blood Reviews
Ehsan Malek, Marcos de Lima, John J Letterio, Byung-Gyu Kim, James H Finke, James J Driscoll, Sergio A Giralt
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous, immature myeloid cell population with the ability to suppress innate and adaptive immune responses that promote tumor growth. MDSCs are increased in patients with multiple myeloma (MM) and have bidirectional interaction with tumors within the MM microenvironment. MM-MDSCs promote MM tumor growth and induce immune suppression; conversely, MM cells induce MDSC development and survival. Although the role of MDSCs in infections, inflammatory diseases and solid tumors has been extensively characterized, their tumor-promoting and immune-suppressive role in MM and the MM microenvironment is only beginning to emerge...
September 2016: Blood Reviews
Zhiwu Dong, Shuang Liang, Jun Hu, Weiyun Jin, Qilin Zhan, Kewen Zhao
Autophagy is an essential metabolic pathway by which the intracellular unwanted materials are digested within lysosomes for cellular homeostasis. It provides energy and building blocks upon starvation or other stresses. Autophagy even contributes to cell death especially under apoptosis incompetent conditions depending on the cellular contexts. Dysfunction of autophagy involves in the initiation and progression of multiple diseases and their treatments. But its principles and clinical applications have not been fully elucidated yet...
September 2016: Blood Reviews
Nicole Carreau, Douglas Tremblay, Michael Savona, Marina Kremyanskaya, John Mascarenhas
Myelofibrosis (MF) and myelodysplastic syndrome (MDS) are hematopoietic stem cell disorders associated with cytopenias and red blood cell (RBC) transfusion dependence. Iron overload (IO) as a consequence of RBC transfusion dependence and its effect on outcomes in MF has not been formally studied. However, IO is a demonstrated poor prognostic feature in patients with MDS and congenital or acquired chronic anemias. Evidence that iron chelation therapy (ICT) reduces the deleterious effects of IO in MDS has led to speculation of benefit in MF...
September 2016: Blood Reviews
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