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Current Opinion in Hematology

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https://www.readbyqxmd.com/read/28632502/targeting-activated-protein-c-to-treat-hemophilia
#1
Stéphanie G I Polderdijk, Trevor P Baglin, James A Huntington
PURPOSE OF REVIEW: Hemophilia is a debilitating disease, marked by frequent, painful bleeding events, joint deterioration and early death. All current treatments consist of i.v. infusions of replacement factor or other procoagulant factors, and are incompletely effective, due in part to the short half-lives of the proteins. An alternative approach is to rebalance hemostasis by inhibiting natural anticoagulant mechanisms. In this article, we explain why activated protein C (APC) is an appropriate and safe target for the treatment of hemophilia...
June 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28604413/single-chain-factor-xii-a-new-form-of-activated-factor-xii
#2
Ivan Ivanov, Anton Matafonov, David Gailani
PURPOSE OF REVIEW: Exposure of blood to foreign surfaces induces reciprocal conversion of the plasma proteins factor XII (fXII) and plasma prekallikrein (PPK) to the proteases α-fXIIa and α-kallikrein. This process, called contact activation, has a range of effects on host defence mechanisms, including promoting coagulation. The nature of the triggering mechanism for contact activation is debated. One hypothesis predicts that fXII has protease activity, either intrinsically or upon surface-binding, that initiates contact activation...
June 9, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28598864/advances-in-vascular-thiol-isomerase-function
#3
Robert Flaumenhaft
PURPOSE OF REVIEW: The present review will provide an overview of several recent advances in the field of vascular thiol isomerase function. RECENT FINDINGS: The initial observation that protein disulfide isomerase (PDI) functions in thrombus formation occurred approximately a decade ago. At the time, there was little understanding regarding how PDI or other vascular thiol isomerases contribute to thrombosis. Although this problem is far from solved, the past few years have seen substantial progress in several areas that will be reviewed in this article...
June 8, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28582314/angiopoietins-and-tie2-in-vascular-inflammation
#4
Samir M Parikh
PURPOSE OF REVIEW: As a subset of the organism-wide reaction to severe infection, the host vascular response has received increasing attention in recent years. The transformation that small blood vessels undergo to facilitate the clearance of pathogens may become harmful to the host if it occurs too broadly or if it is sustained too long. Adverse clinical manifestations of leaky and inflamed blood vessels include edema impairing the function of critical organs and circulatory shock. RECENT FINDINGS: The study suggests that this host vascular response may be both measurable and potentially targetable...
June 2, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28594662/patient-derived-tumor-xenografts-of-lymphoproliferative-disorders-are-they-surrogates-for-the-human-disease
#5
Marco Pizzi, Giorgio Inghirami
PURPOSE OF REVIEW: Patient-derived tumor xenografts (PDTXs) have emerged as powerful platforms in medical oncology. A plethora of PDTXs were generated to study solid cancers, but limited data are as yet available on hematological diseases. The aim of this review is to describe the state of art of lymphoma PDTXs, discussing future directions for the development of integrated/personalized cancer programs. RECENT FINDINGS: In the last decades, several PDTXs of lymphoproliferative disorders have been produced...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28594661/paracrine-regulation-of-normal-and-malignant-hematopoiesis
#6
Wanxing Chai-Ho, John P Chute
PURPOSE OF REVIEW: The paradigm of niche-regulation of hematopoiesis has rapidly and substantially evolved within the last 12 months. Here, we will review the most critical advances in understanding of paracrine regulation of normal and malignant hematopoietic stem cell fate during the past year. RECENT FINDINGS: Several novel paracrine mechanisms have been recently identified, highlighting the function of mesenchymal progenitor cells, osteoprogenitor cells and endothelial cells in regulating hematopoietic stem cell maintenance and regeneration...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28594660/regulation-of-the-hematopoietic-stem-cell-lifecycle-by-the-endothelial-niche
#7
Pradeep Ramalingam, Michael G Poulos, Jason M Butler
PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a vast repertoire of biological processes crucial for HSC maintenance throughout its lifespan. In this review, we will discuss recent findings in endothelial niche-mediated regulation of HSC function during development, aging and regenerative conditions...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28463873/transcriptional-circuits-in-b-cell-transformation
#8
Yeguang Hu, Toshimi Yoshida, Katia Georgopoulos
PURPOSE OF REVIEW: Loss of IKAROS in committed B cell precursors causes a block in differentiation while at the same time augments aberrant cellular properties, such as bone marrow stromal adhesion, self-renewal and resistance to glucocorticoid-mediated cell death. B cell acute lymphoblastic leukaemias originating from these early stages of B cell differentiation and associated with IKAROS mutations share a high-risk cellular phenotype suggesting that deregulation of IKAROS-based mechanisms cause a highly malignant disease process...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28441150/long-non-coding-rnas-in-leukemia-biology-and-clinical-impact
#9
Tim Lammens, Kaat Durinck, Annelynn Wallaert, Frank Speleman, Pieter Van Vlierberghe
PURPOSE OF REVIEW: Over the last years, long non-coding RNAs (lncRNAs) have emerged as putative regulators of malignant hematopoietic development. Here, we review recent literature on the involvement of lncRNAs in leukemia, including their role in driving or sustaining disease and their potential impact on diagnosis, classification, and prognosis. RECENT FINDINGS: Leukemogenesis is a complex process resulting from the accumulation of multiple genetic alterations...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28441149/epigenetic-regulatory-mutations-and-epigenetic-therapy-for-multiple-myeloma
#10
Daphné Dupéré-Richer, Jonathan D Licht
PURPOSE OF REVIEW: Next generation sequencing and large-scale analysis of patient specimens has created a more complete picture of multiple myeloma (MM) revealing that epigenetic deregulation is a prominent factor in MM pathogenesis. RECENT FINDINGS: Over half of MM patients have mutations in genes encoding epigenetic modifier enzymes. The DNA methylation profile of MM is related to the stage of the disease and certain classes of mutations in epigenetic modifiers are more prevalent upon disease relapse, suggesting a role in disease progression...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28426555/creating-artificial-lymphoid-tissues-to-study-immunity-and-hematological-malignancies
#11
Shivem B Shah, Ankur Singh
PURPOSE OF REVIEW: The specialized microenvironments of lymphoid tissue affect immune cell function and progression of disease. However, current animal models are low throughput and a large number of human diseases are difficult to model in animals. Animal models are less amenable to manipulation of tissue niche components, signalling pathways, epigenetics, and genome editing than ex vivo models. On the other hand, conventional 2D cultures lack the physiological relevance to study precise microenvironmental interactions...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28426554/barking-up-the-right-tree-advancing-our-understanding-and-treatment-of-lymphoma-with-a-spontaneous-canine-model
#12
Dania Villarnovo, Angela L McCleary-Wheeler, Kristy L Richards
PURPOSE OF REVIEW: Spontaneous lymphoma in pet dogs is increasingly recognized as an ideal model for studying the disease in humans and for developing new targeted therapeutics for patients. Increasing interest by funding agencies, the private sector, and multidisciplinary academic collaborations between different disciplines and sectors now enables large knowledge gaps to be addressed and provides additional proof-of-concept examples to showcase the significance of the canine model. RECENT FINDINGS: The current review addresses the rationale for a canine lymphoma model including the valuable role it can play in drug development, serving as a link between mouse xenograft models and human clinical trials and the infrastructure that is now in place to facilitate these studies...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28406802/distinct-subtype-distribution-and-somatic-mutation-spectrum-of-lymphomas-in-east-asia
#13
Weicheng Ren, Wei Li, Xiaofei Ye, Hui Liu, Qiang Pan-Hammarström
PURPOSE OF REVIEW: Here, we give an updated overview of the subtype distribution of lymphomas in East Asia and also present the genome sequencing data on two major subtypes of these tumors. RECENT FINDINGS: The distribution of lymphoma types/subtypes among East Asian countries is very similar, with a lower proportion of B-cell malignancies and a higher proportion of T/natural killer (NK)-cell lymphomas as compared to Western populations. Extranodal NK/T-cell lymphoma is more frequently observed in East Asia, whereas follicular lymphoma and chronic lymphocytic leukemia, are proportionally lower...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28402987/new-insights-into-redox-homeostasis-as-a-therapeutic-target-in-b-cell-malignancies
#14
Agnieszka Graczyk-Jarzynka, Radoslaw Zagozdzon, Angelika Muchowicz, Marta Siernicka, Przemyslaw Juszczynski, Malgorzata Firczuk
PURPOSE OF REVIEW: The goal of this review is to summarize recent advances in our understanding of the regulation of redox homeostasis and the subtype-specific role of antioxidant enzymes in B-cell-derived malignancies. Furthermore, it presents selected prooxidative therapeutic strategies against B-cell neoplasms. RECENT FINDINGS: Recent reports have shown that the disturbed redox homeostasis in B-cell malignancies is regulated by cancer-specific signaling pathways and therefore varies between the individual subtypes...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28383341/generating-autologous-hematopoietic-cells-from-human-induced-pluripotent-stem-cells-through-ectopic-expression-of-transcription-factors
#15
Yongsung Hwang, Hal E Broxmeyer, Man Ryul Lee
PURPOSE OF REVIEW: Hematopoietic cell transplantation (HCT) is a successful treatment modality for patients with malignant and nonmalignant disorders, usually when no other treatment option is available. The cells supporting long-term reconstitution after HCT are the hematopoietic stem cells (HSCs), which can be limited in numbers. Moreover, finding an appropriate human leukocyte antigen-matched donor can be problematic. If HSCs can be stably produced in large numbers from autologous or allogeneic cell sources, it would benefit HCT...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28375987/hematopoietic-stem-cells-under-pressure
#16
Miguel Ganuza, Shannon McKinney-Freeman
PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) and progenitors are tasked with maintaining hematopoietic homeostasis in the face of numerous insults and challenges, including infection, inflammation, and exsanguination. HSCs possess the remarkable ability to reconstitute the entire hematopoietic system of an organism whose own hematopoietic system has been ablated. This ability is exploited routinely in the clinic via HSC transplantation (HSCT). Here, we focus on the physiological and molecular bottlenecks overcome by HSCs during transplantation...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28375986/the-new-frontier-of-epigenetic-heterogeneity-in-b-cell-neoplasms
#17
Pilar M Dominguez, Matt Teater, Rita Shaknovich
PURPOSE OF REVIEW: There is mounting evidence that heterogeneity of the epigenome is a feature of many cancers, including B-cell lymphomas, and presents important clinical implications. The purpose of this review is to explain the biological and clinical relevance of this epigenetic phenomenon in B-cell neoplasms. RECENT FINDINGS: Here, we summarize new findings demonstrating that B-cell lymphomas display increased DNA methylation heterogeneity compared to their normal counterparts...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28375985/distinct-functions-of-histone-h3-lysine-4-methyltransferases-in-normal-and-malignant-hematopoiesis
#18
Weiwei Yang, Patricia Ernst
PURPOSE OF REVIEW: Histone H3, lysine 4 (H3K4) methylation is one chromatin modification that defines distinct regulatory states of euchromatin. Mammals express six main histone methyltransferase (HMT) enzymes that modify H3K4 by monomethylation, dimethylation or trimethylation. Recent studies examine roles of some of these HMTs and their cofactors in hematopoiesis and leukemia. We discuss these emerging studies together with prior embryonic stem data, revealing how these enzymes function...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28306669/role-of-shp2-in-hematopoiesis-and-leukemogenesis
#19
Ruchi Pandey, Mallika Saxena, Reuben Kapur
PURPOSE OF REVIEW: SH2 domain-containing tyrosine phosphatase 2 (SHP2), encoded by PTPN11 plays an important role in regulating signaling from cell surface receptor tyrosine kinases during normal development as well as oncogenesis. Herein we review recently discovered roles of SHP2 in normal and aberrant hematopoiesis along with novel strategies to target it. RECENT FINDINGS: Cell autonomous role of SHP2 in normal hematopoiesis and leukemogenesis has long been recognized...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28306668/a-role-for-intracellular-and-extracellular-dek-in-regulating-hematopoiesis
#20
Maegan L Capitano, Hal E Broxmeyer
PURPOSE OF REVIEW: Hematopoietic stem/progenitor cell fate decision during hematopoiesis is regulated by intracellular and extracellular signals such as transcription factors, growth factors, and cell-to-cell interactions. In this review, we explore the function of DEK, a nuclear phosphoprotein, on gene regulation. We also examine how DEK is secreted and internalized by cells, and discuss how both endogenous and extracellular DEK regulates hematopoiesis. Finally, we explore what currently is known about the regulation of DEK during inflammation...
July 2017: Current Opinion in Hematology
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