The new frontier of epigenetic heterogeneity in B-cell neoplasms
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. This plasticity of cytosine methylation manifests both as intertumor and intratumor heterogeneity and is associated with worse prognosis and ...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

New insights into redox homeostasis as a therapeutic target in B-cell malignancies
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. For instance, in a subtype of diffuse large B-cell lymphoma with increased oxidative phosphorylation, ele...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Patient-derived tumor xenografts of lymphoproliferative disorders: are they surrogates for the human disease?
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. Most studies focused on acute lymphoblastic leukemias, but consistent results have recently been obtained also for in...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Creating artificial lymphoid tissues to study immunity and hematological malignancies
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. Thus, artificial tissues are being developed to study these interactions in the context of immune devel...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Distinct subtype distribution and somatic mutation spectrum of lymphomas in East Asia
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. The incidence rate of lymph...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Barking up the right tree: advancing our understanding and treatment of lymphoma with a spontaneous canine model
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 deve...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Long non-coding RNAs in leukemia: biology and clinical impact
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. Over the last years, advances in high-throughput sequencing and transcriptome profiling have enabled the identification of lncRNAs involved in leukemia developme...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Transcriptional circuits in B cell transformation
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. Recent studies: Recent studies show that IKAROS is critical for the activity of super-enhan...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma
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. Many small molecules targeting regulators of epigenetic machinery have been de...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Paracrine regulation of normal and malignant hematopoiesis
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. Similarly, niche-driven inflammatory states, paracrine mechanisms, exosomes, ...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Distinct functions of histone H3, lysine 4 methyltransferases in normal and malignant hematopoiesis
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. Recent findings: Murine models have been employed to conditionally or constitutively knockout HMTs (MLL1/KMT2A, MLL2/KMT2B, MLL3/KMT2C...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Hematopoietic stem cells under pressure
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. Recent findings: During transplantation, HSCs encounter a damaged bone m...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Role of SHP2 in hematopoiesis and leukemogenesis
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. The review will discuss the newly discovered role of SHP2 in lineage specific differentiation. Recently, a noncell autonomous role of oncogenic SHP2 has...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

A role for intracellular and extracellular DEK in regulating hematopoiesis
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. Recent findings: DEK negatively regulates the proliferation of early myeloid ...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Regulation of the hematopoietic stem cell lifecycle by the endothelial niche
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. Recent findings: Studies employing genetic vascular mod...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Generating autologous hematopoietic cells from human-induced pluripotent stem cells through ectopic expression of transcription factors
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. Induced pluripotent stem cells (iPSCs) established from patients’ own somatic cells c...
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - June 8, 2017 Category: Hematology Tags: Editorial Introductions Source Type: research

New biomarkers and imaging approaches for the diagnosis of deep venous thrombosis
Purpose of review: Symptoms suggestive of deep vein thrombosis (DVT) are extremely common in clinical practice, but unfortunately nonspecific. In both ambulatory and inpatient settings, clinicians are often tasked with evaluating these concerns. Here, we review the most recent advances in biomarkers and imaging to diagnose lower extremity DVT. Recent findings: The modified Wells score remains the most supported clinical decision rule for risk stratifying patients. In uncomplicated patients, the D-dimer can be utilized with risk stratification to reasonably exclude lower extremity DVT in some patients. Although numerous bi...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

P-selectin glycoprotein ligand-1 in T cells
Purpose of review: We review P-selectin glycoprotein ligand-1 (PSGL-1) as a selectin and chemokine-binding adhesion molecule. PSGL-1 is widely studied in neutrophils. Here, we focus on T cells, because PSGL-1 was recently described as a major immunomodulatory molecule during viral infection. PSGL-1 also plays a crucial role in T-cell homeostasis by binding to lymphoid chemokines, and can induce tolerance by enhancing the functions of regulatory T cells. Recent findings: PSGL-1 was originally described as a leukocyte ligand for P-selectin, but it is actually a ligand for all selectins (P-, L- and E-selectin), binds chemoki...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Endothelial cell disease: emerging knowledge from cerebral cavernous malformations
Purpose of review: Endothelial cells dysfunctions are crucial determinants of several human diseases. We review here the most recent reports on endothelial cell defects in cerebral cavernous malformations (CCMs), particularly focusing on adherens junctions. CCM is a vascular disease that affects specifically the venous microvessels of the central nervous system and which is caused by loss-of-function mutation in any one of the three CCM genes (CCM1, 2 or 3) in endothelial cells. The phenotypic result of these mutations are focal vascular malformations that are permeable and fragile causing neurological symptoms and occasio...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Rap1 in endothelial biology
Purpose of review: Ubiquitously-expressed small GTPase Rap1 is a key modulator of integrin- and cadherin-regulated processes. In endothelium, Rap1 promotes angiogenesis and endothelial barrier function, acting downstream from cAMP-activated Rap1GEF, Epac. Recent in-vivo studies in mouse models have provided more information about the physiological role of Rap1 in vessel development and after birth under normal and pathologic conditions. Important molecular details of dynamic regulation of endothelial barrier are uncovered. Recent findings: Rap1 is not essential for initial vessel formation but is critical for vessel stabi...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Endothelial cell metabolism: an update anno 2017
Purpose of review: Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications. Recent findings: Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO). Glycolysis is essential as endothelial cells primarily rely on this pathway for ATP production. 6-Phosphof...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Wnt signaling in the vessel wall
Purpose of review: Wnt signaling plays a crucial role during embryogenesis. In an adult, Wnt is mainly associated to cellular proliferation and differentiation mechanisms. Recent data suggest that Wnt signaling is involved in the pathophysiology of atherosclerosis. However, the roles of Wnt signaling pathways in the vessel wall are poorly understood. This review outlines recent discoveries in understanding the role of Wnt pathways in healthy and atherosclerotic vessels. Recent findings: In the last years, the involvement of both canonical and noncanonical Wnt pathways in the development of atherosclerotic lesions has been...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Krüppel-like factors in endothelial cell biology
Purpose of review: Krüppel-like factors (KLFs) are a family of transcription factors that regulate integral functions of endothelial cells including inflammation, proliferation, growth, apoptosis, cell differentiation and plasticity, and migration. This review will focus on the role of KLFs in physiological activity and their loss in vascular pathology. Recent findings: New studies have pointed at the role of microRNAs as repressors of KLFs in atherosclerotic areas providing another level of signaling regulation of KLFs. Summary: KLFs are important regulators of almost all facets of endothelial biology, making them ...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

An enlightening year in vascular biology
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

RNA splicing during terminal erythropoiesis
Purpose of review: Erythroid progenitors must accurately and efficiently splice thousands of pre-mRNAs as the cells undergo extensive changes in gene expression and cellular remodeling during terminal erythropoiesis. Alternative splicing choices are governed by interactions between RNA binding proteins and cis-regulatory binding motifs in the RNA. This review will focus on recent studies that define the genome-wide scope of splicing in erythroblasts and discuss what is known about its regulation. Recent findings: RNA-seq analysis of highly purified erythroblast populations has revealed an extensive program of alternative ...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Molecular mechanisms that mediate invasion and egress of malaria parasites from red blood cells
Purpose of review: Malaria parasites invade and multiply in diverse host cells during their complex life cycle. Some blood stage parasites transform into male and female gametocytes that are transmitted by female anopheline mosquitoes. The gametocytes are activated in the mosquito midgut to form male and female gametes, which egress from RBCs to mate and form a zygote. Here, we will review our current understanding of the molecular mechanisms that mediate invasion and egress by malaria parasites at different life cycle stages. Recent findings: A number of key effector molecules such as parasite protein ligands for recepto...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Acute hepatic and erythropoietic porphyrias: from ALA synthases 1 and 2 to new molecular bases and treatments
Purpose of review: Many studies over the past decade have together identified new genes including modifier genes and new regulation and pathophysiological mechanisms in inherited inborn diseases of the heme biosynthetic pathway. A new porphyria has been characterized: X-linked protoporphyria and the perspective to have innovative treatment at very short-term became a reality. We will summarize how recent data on both ALAS1 and ALAS2 have informed our understanding of disease pathogenesis with an emphasis on how this information may contribute to new therapeutic strategies. Recent findings: The development of clinical and ...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Dyserythropoiesis of myelodysplastic syndromes
Purpose of review: Myelodysplastic syndromes (MDS) are heterogeneous diseases of the hematopoietic stem cell in the elderly. Anemia is the main symptom that mostly correlates with dysplastic erythropoiesis in the bone marrow. We will review the recent advances in understanding the diverse mechanisms of dyserythropoiesis. Recent findings: Dyserythropoiesis defined as 10% dysplastic erythroid cells in the bone marrow is found in more than 80% of early MDS. Immature erythroblasts accumulate at the expense of mature erythroblasts due to differentiation arrest and apoptosis. In early MDS with dyserythropoiesis, caspase-depende...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Orchestration of late events in erythropoiesis by KLF1/EKLF
Purpose of review: Transcriptional regulators provide the molecular and biochemical basis for the cell specific properties and characteristics that follow from their central role in establishing tissue-restricted expression. Precise and sequential control of terminal cell divisions, nuclear condensation, and enucleation are defining characteristics within erythropoietic differentiation. This review is focused on KLF1, a central global regulator of this process. Recent findings: Studies in the past year have brought a number of proteins that are targets of KLF1 regulation into focus with respect to their roles in terminal ...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Genetic control of erythropoiesis
Purpose of review: The discovery of several genetic variants associated with erythroid traits and subsequent elucidation of their functional mechanisms are exemplars of the power of the new genetic and genomic technology. The present review highlights findings from recent genetic studies related to the control of erythropoiesis and dyserythropoiesis, and fetal hemoglobin, an erythroid-related trait. Recent findings: Identification of the genetic modulators of erythropoiesis involved two approaches: genome-wide association studies (GWASs) using single nucleotide polymorphism (SNP) arrays that revealed the common genetic va...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Maintenance and regulation of asymmetric phospholipid distribution in human erythrocyte membranes: implications for erythrocyte functions
Purpose of review: The article summarizes new insights into the molecular mechanisms for the maintenance and regulation of the asymmetric distribution of phospholipids in human erythrocyte membranes. We focus on phosphatidylserine, which is primarily found in the inner leaflet of the membrane lipid bilayer under low Ca2+ conditions (1 μmol/l), when cells become senescent. Clarification of the molecular basis of phosphatidylserine flipping and scrambling is important for addressing long-standing questions regarding phosphatidylserine functions. Recent findings: ATP11C, a P-IV ATPase, has been identified as a major fli...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Characterization, regulation, and targeting of erythroid progenitors in normal and disordered human erythropoiesis
Purpose of review: The erythroid progenitors burst-forming unit-erythroid and colony-forming unit-erythroid have a critical role in erythropoiesis. These cells represent a heterogeneous and poorly characterized population with modifiable self-renewal, proliferation and differentiation capabilities. This review focuses on the current state of erythroid progenitor biology with regard to immunophenotypic identification and regulatory programs. In addition, we will discuss the therapeutic implications of using these erythroid progenitors as pharmacologic targets. Recent findings: Erythroid progenitors are classically characte...
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 5, 2017 Category: Hematology Tags: Editorial Introductions Source Type: research

Making the most of hypomethylating agents in myelodysplastic syndromes
Purpose of review: Hypomethylating agents (HMA) are the preferred therapy for patients with higher risk myelodysplastic syndromes (MDS) and an alternative therapeutic strategy for older patients with acute myeloid leukemia. These agents have improved both survival and quality of life, but results overall remain poor. The purpose of this review is to highlight recent developments in clinical research with HMA in MDS/acute myeloid leukemia over the last year. Recent findings: Combination of HMA with B-cell lymphoma-2 inhibitors, hedgehog inhibitors, and a variety of other agents are underway, as are further studies with ref...
Source: Current Opinion in Hematology - March 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Therapy-related myeloid neoplasms
Purpose of review: Advances in the genetic characterization of patients with therapy-related myeloid neoplasms (t-MNs) have changed our understanding of the pathogenesis of these diseases. In addition, extensive sequencing studies have identified recurrent mutations with diagnostic and prognostic impact. Thus, the revised version of the WHO classification combines therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML) in the one entity of t-MNs because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Recent findings: Fifte...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Revisiting erythroleukemia
Purpose of review: The 2016 WHO classification of hematopoietic and lymphoid neoplasms alters the diagnostic criteria for erythroleukemia, including eliminating the erythroid/myeloid type of acute erythroleukemia, which was a prior subcategory of acute myeloid leukemia, not otherwise specified. Only pure erythroid leukemia remains in the WHO classification. This review will summarize the literature that contributed to that classification change as well as recent literature on the significance of the change. Recent findings: There is now a large body of literature on the negative prognostic impact of erythroid predominance...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Mixed-phenotype acute leukemia: current challenges in diagnosis and therapy
Purpose of review: Mixed-phenotype acute leukemia (MPAL) is a rare disease that poses many diagnostic and therapeutic challenges. Patients with MPAL are considered to have poor outcomes. The difficulties in classifying this leukemia, the lack of prospectively collected data concerning therapeutic outcomes, and rare incidence result in much uncertainty as to the best approach for patients with MPAL. Recent findings: Recent studies demonstrated that most MPALs are associated with cytogenetic abnormalities; genetic sequencing studies disclose a high frequency of somatic mutations in genes encoding epigenetic regulators, tumo...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Should patients with acute myeloid leukemia and measurable residual disease be transplanted in first complete remission?
Purpose of review: Measurable (‘minimal’) residual disease in acute myeloid leukemia during first complete morphologic remission (MRDpos CR1) identifies patients with particularly high relapse risk and short survival. Here, we examine the evidence regarding optimal postremission treatment strategy for such patients. Recent findings: With chemotherapy alone or chemotherapy/autologous hematopoietic cell transplantation (HCT), disease recurrence appears inevitable in patients with MRDpos CR1. Nonrandomized studies indicate that allogeneic HCT improves outcomes over chemotherapy and/or autologous HCT, although rel...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Can any patients with chronic myeloid leukemia outside of a clinical trial have their tyrosine kinase inhibitor discontinued?
This article critically appraises the state of treatment-free remission as a strategy for patients with chronic myeloid leukemia (CML) in deep remission after therapy with tyrosine kinase inhibitors (TKIs). Recent findings: Approximately half of patients with CML defined fairly narrowly by trial criteria – TKI sensitive, in deep molecular remission for a defined period – can successfully maintain protective levels of response after TKI cessation. Those who cannot appear at very low risk of disease control loss and can promptly regain remission with TKI resumption. Increasing numbers of patients followed longer...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

‘JAK–ing’ up the treatment of primary myelofibrosis: building better combination strategies
Purpose of review: The article discusses the promising agents that are approved or currently under investigation for the treatment of myelofibrosis and reviews the ongoing Janus kinase (JAK) inhibitors–based combinatorial strategies in this setting. Recent findings: Myelofibrosis is a Philadelphia-negative myeloproliferative neoplasm with constitutive JAK/STAT activation. The JAK-inhibitor ruxolitinib is the only approved drug for this disease in the United States and Europe based on two randomized phase III studies that demonstrated clinically meaningful reduction in spleen size, improvement in symptoms, quality of...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Management of venous thromboembolism in myeloproliferative neoplasms
Purpose of review: Venous thromboembolism is frequent in chronic myeloproliferative neoplasms (MPN). The current strategy for its management includes cytoreductive therapy and antithrombotic prophylaxis, but many issues remain uncertain. In this review, the risk factors and prevention of recurrences will be discussed. Recent findings: Around one-third of patients with polycythemia vera and essential thrombocythemia experience a major thrombosis at diagnosis or during follow-up. According to the European Leukemia Net guidelines, these patients must be included in the high-risk group for thrombotic recurrence and should be ...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

What are the most promising new agents in acute myeloid leukemia?
Purpose of review: Although the treatment paradigm for acute myeloid leukemia (AML) had been largely unchanged for many years, in-depth molecular characterization has revolutionized our understanding of mutations that drive the disease, subsequently serving to guide current clinical investigation. Furthermore, recent advances in the field have highlighted the importance of optimizing known efficacious agents by improving drug delivery or bypassing resistance mechanisms. The current status of novel agents which are shaping the clinical management of AML patients are summarized in this review. Recent findings: Practice chan...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Innovative strategies for adverse karyotype acute myeloid leukemia
Purpose of review: Adverse karyotype acute myeloid leukemia is a disease particularly of older patients, but also observed in younger patients. Despite all efforts, standard chemotherapy is still generally applied in fit patients, as already for decades, and for nearly all different subtypes of acute myeloid leukemia. Lack of more specifically targeted therapy and the often older age of the patients are complicating treatment, and in the subgroup of patients achieving a complete remission, the strikingly high frequency of relapse is a characteristic of this disease. This review aims to give an overview of current treatment...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Making the most of hypomethylating agents in myelodysplastic syndrome
Purpose of review: Hypomethylating agents (HMA) are the preferred therapy for patients with higher risk myelodysplastic syndromes (MDS) and an alternative therapeutic strategy for older patients with acute myeloid leukemia. These agents have improved both survival and quality of life, but results overall remain poor. The purpose of this review is to highlight recent developments in clinical research with HMA in MDS/acute myeloid leukemia over the last year. Recent findings: Combination of HMA with B-cell lymphoma-2 inhibitors, hedgehog inhibitors, and a variety of other agents are underway, as are further studies with ref...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Implications of molecular genetic diversity in myelodysplastic syndromes
Purpose of review: Myelodysplastic syndromes (MDS) have remarkably diverse somatic mutation patterns that can be challenging to interpret clinically. Yet, genetic information is increasingly available to physicians. This review will examine several implications of genetic diversity in MDS. Recent findings: Somatic mutations can serve as clinically relevant biomarkers in MDS. Molecular subtypes may exist that share clinical features including risk of progression to acute myeloid leukemia, response to treatment, and overall survival. Several mutated genes are known to have prognostic value that is independent of common risk...
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - February 1, 2017 Category: Hematology Tags: Editorial Introduction Source Type: research

Allogeneic hematopoietic stem cell transplantation for dyskeratosis congenita: erratum
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - December 29, 2016 Category: Hematology Tags: Erratum Source Type: research

Consequences of extracellular trap formation in sepsis
Purpose of review: This review will focus on in-vivo findings derived from animal models of sepsis regarding the trapping role of neutrophil extracellular traps (NETs) which is difficult to assess ex vivo. The NETotic response of neutrophils at sites of sterile injury or autoimmune disease is destructive as no antimicrobial advantage to the host is realized and dampening NETosis is largely beneficial. In early stages of local infection or in sepsis, the trapping function of NETs may help abscess formation and limit microbial dissemination. Recent findings: The trapping function of NETs limits bacterial dissemination keepi...
Source: Current Opinion in Hematology - December 29, 2016 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Mechanism of granuloma formation in sarcoidosis
Purpose of review: The formation of noncaseating granuloma is a hallmark of pulmonary sarcoidosis. This review summarizes recent progress made to explain the cellular dynamics within the granuloma structure that may considerably differ between the two clinically distinct variants, that is, acute and chronic sarcoidosis. Recent findings: Compelling evidence exists that in acute but not chronic sarcoidosis CD4+ T lymphocytes specifically recognizing the auto-antigen vimentin on human leukocyte antigen-DR3 molecules accumulate in sarcoid granuloma. These so-called TH17.1 cells produce high amounts of the TH17-related cytokin...
Source: Current Opinion in Hematology - December 29, 2016 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research