Biophysical and rheological biomarkers of red blood cell physiology and pathophysiology
Purpose of review
This review summarizes the significant biophysical and rheological aspects of red blood cell physiology and pathophysiology in relation to recent advances in microfluidic biomarker assays and emerging targeted or curative intent therapies.
Recent findings
Alterations in red cell biophysical properties and blood rheology have been associated with numerous hematologic and circulatory disorders. Recent advances in biomarker assays enable effective assessment of these biophysical and rheological properties in normoxia or physiological hypoxia in a clinically meaningful way. There are emerging targe...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research
‘Enhancing’ red cell fate through epigenetic mechanisms
Purpose of review
Transcription of erythroid-specific genes is regulated by the three-dimensional (3D) structure and composition of chromatin, which dynamically changes during erythroid differentiation. Chromatin organization and dynamics are regulated by several epigenetic mechanisms involving DNA (de-)methylation, posttranslational modifications (PTMs) of histones, chromatin-associated structural proteins, and higher-order structural changes and interactions. This review addresses examples of recent developments in several areas delineating the interface of chromatin regulation and erythroid-specific lineage transcri...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Novel developments in chronic myeloid leukaemia
Purpose of review
Despite unprecedented challenges during the preceding year, there have been a wide range of significant advances in the field of chronic myeloid leukaemia. In this review article we highlight papers reporting on some of the most important developments over the last year, both with regards to the clinical management of patients with chronic myeloid leukaemia, as well as studies that help to increase our understanding of the pathophysiology of the disease. We have performed a PubMed search to identify important papers and abstracts listed over the last year and have included additional papers published ...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research
Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission
Purpose of review
Maintenance therapy for acute myeloid leukemia (AML) has been studied for decades with mixed results. However, the application of modern agents has renewed interest and the recent data from randomized trials has provided evidence for the use of maintenance therapy in certain populations of AML patients.
Recent findings
Unselected patients are unlikely to benefit from maintenance therapy as has been previously and consistently demonstrated. The increasing availability of newer and targeted agents like oral hypomethylating agents, protein modifiers, as well as FLT3, IDH1/2 BCL-2 and immune checkp...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research
Prognostic mutation constellations in acute myeloid leukaemia and myelodysplastic syndrome
Purpose of review
In the past decade, numerous studies analysing the genome and transcriptome of large cohorts of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients have substantially improved our knowledge of the genetic landscape of these diseases with the identification of heterogeneous constellations of germline and somatic mutations with prognostic and therapeutic relevance. However, inclusion of integrated genetic data into classification schema is still far from a reality. The purpose of this review is to summarize recent insights into the prevalence, pathogenic role, clonal architecture, ...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research
Clonal hematopoiesis in hematopoietic stem cell transplantation
Purpose of review
Clonal hematopoiesis (CH) is characterized by the acquisition of somatic mutations and subsequent expansion of mutated hematopoietic stem and progenitor cell (HSPC) clones without clinical evidence for a hematologic neoplasm. The prevalence of CH continuously increases with age reaching double-digit percentages in individuals>60 years. CH is associated with an increased risk for hematologic neoplasms and cardiovascular disease. We will review recent efforts to investigate how CH influences patient outcomes in hematopoietic stem cell transplantation – both autologous (ASCT) and allogeneic (allo-HSCT)...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research
Germline mutations in MDS/AML predisposition disorders
Purpose of review
Recognition of hereditary hematopoietic malignancies impacts patient management as well as health surveillance strategies for the patient and relatives who share the causative DNA variant. In this review, barriers to the diagnosis and management of patients are outlined.
Recent findings
Increasingly, individuals are being recognized as having germline predisposition to hematopoietic malignancies. Clinical testing for these syndromes is difficult for most clinicians given the need to send true germline samples and the lack of standardization in the field with regard to which genes are covered an...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research
The N6-methyladenosine RNA modification in acute myeloid leukemia
Purpose of review
In recent years, the N6-methyladenosine (m6A) modification of RNA has been shown to play an important role in the development of acute myeloid leukemia (AML) and the maintenance of leukemic stem cells (LSCs). In this review we summarise the recent findings in the field of epitranscriptomics related to m6A and its relevance in AML.
Recent findings
Recent studies have focused on the role of m6A regulators in the development of AML and their potential as translational targets. The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-co...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research
Therapeutic approaches targeting splicing factor mutations in myelodysplastic syndromes and acute myeloid leukemia
Purpose of review
Mutations in components of the spliceosome are the most common acquired lesions in myelodysplastic syndromes (MDS) and are frequently identified in other myeloid malignancies with a high rate of progression to acute myeloid leukemia (AML) including chronic myelomonocytic leukemia and primary myelofibrosis. The only curative option for these disorders remains allogeneic stem-cell transplantation, which is associated with high morbidity and mortality in these patients. The purpose of this review is to highlight the recent therapeutic developments and strategies being pursued for clinical benefit in spli...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research
Editorial: Do not lose focus on myeloid biology in the era of COVID-19
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Genetic heterogeneity and clonal evolution in acute myeloid leukemia
Purpose of review
Clonal heterogeneity is a significant obstacle to successful treatment of patients with acute myeloid leukemia (AML). Here, we review new advances in the understanding of genetic heterogeneity in AML using single-cell DNA-sequencing technology.
Recent findings
New genomics and immunologic discovery tools have provided single-cell resolution maps of the clonal architecture of AML. The use of these technologies reveals the mutational landscape of AML at diagnosis, during treatment, and at relapse has an enormous degree of clonal complexity and diversity that is poised to adapt and evolve under en...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research
Human hematopoiesis: aging and leukemogenic risk
Purpose of review
Our understanding of the effects of aging on human hematopoiesis has advanced significantly in recent years, yet the full ramifications of these findings are not fully understood. This review summarizes these findings and discusses their implication as they relate to malignant hematopoiesis.
Recent findings
With human aging there is an impaired immune response, loss of hematopoietic stem cell (HSC) function, increase in clonal hematopoiesis, and higher frequency of myeloid malignancies. Although murine models have implicated abnormalities in DNA damage repair, autophagy, metabolism, and epigene...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research
Studying clonal evolution of myeloid malignancies using induced pluripotent stem cells
Purpose of review
Myeloid malignancies comprise a spectrum of genetically heterogeneous disorders marked by the stepwise acquisition of somatic mutations and clonal evolution. The blood and bone marrow of patients typically consists of a mix of different clones and subclones along the path of clonal evolution that cannot be deconvoluted with most current approaches. Here, we review the application of induced pluripotent stem cell (iPSC) technology to the study of the clonal architecture and clonal evolution of these diseases, focusing on myelodysplastic syndromes and acute myeloid leukemia.
Recent findings
Repro...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research
