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Current Opinion in Hematology

Dipty Jain, Dipika Mohanty
PURPOSE OF REVIEW: In the past, milder clinical manifestations of sickle cell disease (SCD) have been described from India. However, recent data from some parts of India suggest that the severity of the disease can be compared to that of African phenotypes. This review therefore describes the varied clinical manifestation of SCD, the success of newborn screening programme, prenatal diagnosis and low dose hydroxyurea therapy in India. RECENT FINDINGS: The varied clinical manifestations such as anemia, vaso-occlusive crisis, acute chest syndrome, renal involvement, stroke and so on vary from one part of the country to the other and also among different communities of India...
February 19, 2018: Current Opinion in Hematology
Hui Zhong, Karina Yazdanbakhsh
PURPOSE OF REVIEW: Hemolytic anemias caused by premature destruction of red blood cells occur in many disorders including hemoglobinopathies, autoimmune conditions, during infection or following reaction to drugs or transfusions. Recent studies which will be reviewed here have uncovered several novel mechanisms by which hemolysis can alter immunological functions and increase the risk of severe complications in hemolytic disorders. RECENT FINDINGS: Plasma-free heme can induce the formation of neutrophil extracellular traps (NETs) through reactive oxygen species signaling...
February 15, 2018: Current Opinion in Hematology
Caroline C Philpott
PURPOSE OF REVIEW: Terminal differentiation of erythropoietic progenitors requires the rapid accumulation of large amounts of iron, which is transported to the mitochondria, where it is incorporated into heme. Ferritin is the sole site of iron storage present in the cytosol. Yet the role of iron accumulation into ferritin in the context of red cell development had not been clearly defined. Early studies indicated that at the onset of terminal differentiation, iron initially accumulates in ferritin and precedes heme synthesis...
February 15, 2018: Current Opinion in Hematology
Usha R Pendurthi, L Vijaya Mohan Rao
PURPOSE OF REVIEW: Endothelial cell protein C receptor (EPCR), a transmembrane glycoprotein present on the surface of endothelial cells and other cell types, is an essential component of the protein C (PC) anticoagulant system. EPCR is also shown to play a critical role in mediating activated protein C (APC)-induced cytoprotective signaling. The purpose of this review is to outline the mechanisms of EPCR-dependent cell signaling and discuss recent findings made in this area. RECENT FINDINGS: Recent studies showed that the cleavage of protease-activated receptor (PAR)1 at a noncanonical site by APC-EPCR or the canonical site by thrombin when PC occupies EPCR induces β-arrestin-2-mediated biased cytoprotective signaling...
February 15, 2018: Current Opinion in Hematology
Wade W Sugden, Arndt F Siekmann
PURPOSE OF REVIEW: Mutations in the Endoglin (Eng) gene, an auxiliary receptor in the transforming growth factor beta (TGFβ)-superfamily signaling pathway, are responsible for the human vascular disorder hereditary hemorrhagic telangiectasia (HHT) type 1, characterized in part by blood vessel enlargement. A growing body of work has uncovered an autonomous role for Eng in endothelial cells. We will highlight the influence of Eng on distinct cellular behaviors, such as migration and shape control, which are ultimately important for the assignment of proper blood vessel diameters...
February 12, 2018: Current Opinion in Hematology
Yazan M Abbas, Ashley M Toye, John L Rubinstein, Reinhart A F Reithmeier
PURPOSE OF REVIEW: Current research on the human band 3 glycoprotein, the red cell chloride/bicarbonate anion exchanger (AE1), is highlighted and placed within a structural context. RECENT FINDINGS: The determination of the crystal structure of the membrane domain of human band 3, the founding member of the solute carrier 4 (SLC4) family of bicarbonate transporters, is a major breakthrough toward understanding the mechanism of action of this membrane transport protein, its interaction with partner proteins, and how mutations linked to disease affect its ability to fold and function...
February 12, 2018: Current Opinion in Hematology
Li Zhang
PURPOSE OF REVIEW: Macrophages are generally believed to originate entirely from the bone marrow; however, this paradigm is challenged by the discovery of yolk-sac-derived resident macrophages. Here, we provide an overview of recent advances in the ontogeny and function of resident macrophages. RECENT FINDINGS: Macrophage precursors from three distinct embryonic sources (yolk sac, fetal liver and bone marrow) are found to colonize various tissues via the blood circulation early during embryogenesis until shortly after birth...
February 12, 2018: Current Opinion in Hematology
Ryota L Matsuoka, Didier Y R Stainier
PURPOSE OF REVIEW: Zebrafish has provided a powerful platform to study vascular biology over the past 25 years, owing to their distinct advantages for imaging and genetic manipulation. In this review, we summarize recent progress in vascular biology with particular emphasis on vascular development in zebrafish. RECENT FINDINGS: The advent of transcription activator-like effector nuclease and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 genome-editing technologies has dramatically facilitated reverse genetic approaches in zebrafish, as in other models...
February 12, 2018: Current Opinion in Hematology
Andrea A Perreault, Bryan J Venters
PURPOSE OF REVIEW: Erythropoietin (EPO) is necessary and sufficient to trigger dynamic transcriptional patterns that drive the differentiation of erythroid precursor cells into mature, enucleated red cells. Because the molecular cloning and Food and Drug Administration approval for the therapeutic use of EPO over 30 years ago, a detailed understanding of how EPO works has advanced substantially. Yet, the precise epigenetic and transcriptional mechanisms by which EPO signaling controls erythroid expression patterns remains poorly understood...
January 30, 2018: Current Opinion in Hematology
Chezi Ganzel, Jacob M Rowe
PURPOSE OF REVIEW: Autologous hematopoietic cell transplantation (auto-HCT) has been evaluated as a consolidation treatment for acute myeloid leukemia (AML) in the 1980s and 1990s. These prospective studies from large trials compared auto-HCT with chemotherapy. A comparison was made also with allogeneic hematopoietic cell transplantation (allo-HCT). These studies reported a lower relapse rate with auto-HCT compared with chemotherapy, but without impact on the overall survival. A high transplant-related mortality in that era confounded the relevance of these data...
January 10, 2018: Current Opinion in Hematology
Moshe Yeshurun, Ofir Wolach
PURPOSE OF REVIEW: Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative therapy for patients with acute myeloid leukemia. Despite the associated graft-versus-leukemia effect, leukemia relapse remains the most common cause of treatment failure after alloHCT. Here, we review the available data on whether there is an advantage in providing pretransplant consolidation chemotherapy prior to alloHCT. RECENT FINDINGS: Randomized controlled studies are lacking...
December 27, 2017: Current Opinion in Hematology
Kamal Menghrajani, Martin S Tallman
PURPOSE OF REVIEW: Treatments for acute myeloid leukemia (AML) had remained essentially unchanged for several years; however, the advent of molecular testing has generated insight into the biology of this disease which is now being translated into clinical practice. New treatment strategies which improve drug delivery and exploit cellular targets are changing the landscape of how we treat this disease. RECENT FINDINGS: Induction therapy is in the process of changing for several patient populations...
December 27, 2017: Current Opinion in Hematology
Aaron D Viny, Ross L Levine
PURPOSE OF REVIEW: Recurrent loss of function mutations within genes of the cohesin complex have been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). STAG2 is the most commonly mutated cohesin member in AML as well as solid tumors. STAG2 is recurrently, mutated in Ewing's Sarcoma, bladder cancer, and glioblastoma, and is one of only ten genes known to be recurrently mutated in over four distinct tissue types of human cancer RECENT FINDINGS: The cohesin complex, a multiprotein ring, is canonically known to align and stabilize replicated chromosomes prior to cell division...
December 22, 2017: Current Opinion in Hematology
Robert P Hasserjian
PURPOSE OF REVIEW: This review highlights the main changes in the revised 2016 WHO classification of myeloid neoplasms (published in 2017) that impact diagnosis and ultimately impact management of patients with these diseases. RECENT FINDINGS: The revision was based on data accumulated since the 2008 WHO classification, much of which relate to new molecular genetic information about these neoplasms. This massive recent influx of data concerning the significance of pathogenic mutations has affected all myeloid neoplasm categories...
December 18, 2017: Current Opinion in Hematology
Rita Assi, Hagop Kantarjian, Farhad Ravandi, Naval Daver
PURPOSE OF REVIEW: This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). RECENT FINDINGS: The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML...
December 4, 2017: Current Opinion in Hematology
(no author information available yet)
No abstract text is available yet for this article.
March 2018: Current Opinion in Hematology
Vivek A Upadhyay, Amir T Fathi
PURPOSE OF REVIEW: This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution. RECENT FINDINGS: We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including '7+3 Plus' combinations...
March 2018: Current Opinion in Hematology
Jia Hau Liu, Christopher G Kanakry, Leo Luznik
PURPOSE OF REVIEW: Haploidentical stem cell transplantation (Haplo SCT) and umbilical cord blood stem cell transplantation (UCB SCT) have emerged over the past two to three decades as viable sources of alternative donor SCT when a human leukocyte antigen matched donor is not available. However, which of these two donor types is optimal for patients with leukemia in need of allografting is unknown. RECENT FINDINGS: For patients with acute leukemia, results of UCB SCT have been improved by the use of double umbilical cord units and emerging ex-vivo expansion technologies...
March 2018: Current Opinion in Hematology
Alexander E Perl
PURPOSE OF REVIEW: Precious few drugs were successfully developed for acute myeloid leukemia (AML) over the past decades, despite a dramatic expansion of our understanding of its molecular underpinnings during this time. Then in 2017, a wave of new drugs suddenly became approved. This review serves to introduce the newly available drugs, discuss their impact upon therapy, and highlight additional novel agents that are waiting in the wings. RECENT FINDINGS: Newly approved agents in AML include a tyrosine kinase inhibitor for patients with FMS-like tyrosine kinase 3 (FLT3) mutations, an inhibitor of mutant isocitrate dehydrogenase (IDH2), and two novel agents using antibody-delivered or liposome-delivered cytotoxics...
March 2018: Current Opinion in Hematology
Chetasi Talati, Javier Pinilla-Ibarz
PURPOSE OF REVIEW: Chronic myeloid leukemia (CML) is hallmarked by the presence of fusion protein kinase derived from a reciprocal translocation between chromosome 9 and 22, breakpoint cluster region (BCR)-Abelson leukemia virus (ABL) 1, causing aberrant regulation of the downstream pathways leading to unchecked CML leukemia stem cells (LSCs) proliferation. Since the discovery of tyrosine kinase inhibitors (TKI), CML, once a fatal disease, has become a chronic illness if managed appropriately...
March 2018: Current Opinion in Hematology
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