p53 involvement in clonal hematopoiesis of indeterminate potential
Purpose of review
Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and occurs when a single mutant hematopoietic stem cell (HSC) contributes to a significant clonal proportion of mature blood lineages. Somatic mutations in the TP53 gene, which encodes the tumor suppressor protein p53, rank in the top five among genes that were mutated in CHIP. This review focuses on mechanisms by which mutant p53 promotes CHIP progression and drives the pathogenesis of hematological malignancies, including myelodysplastic syndromes, and acute myeloid leukemia.
Recent findings
TP53 was frequently mutated in ind...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research
Mitochondrial metabolism and the maintenance of hematopoietic stem cell quiescence
Purpose of review
Hematopoietic stem cells (HSCs) are characterized by a potent multilineage regenerative capability that is dependent on their quiescence property. In the past few decades, researchers have found many intrinsic and niche-derived factors that can regulate HSCs, whereas how to precisely control HSC behaviors remains elusive. Recently, mitochondrial metabolism has been shown to be involved in the regulation of HSC biology. The purpose of this review is to overview recent advances in the relationship between mitochondrial metabolism and maintenance of HSC quiescence.
Recent findings
On the basis of fact t...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research
Growing old in the age of heterogeneity: the perils of shifting clonality
Purpose of review
Hematopoietic stem cells (HSC) are functionally heterogeneous in a clone-specific manner. The complexity of that heterogeneous mix of cells is progressively lost with age as a myeloid-dominant hematopoietic system is established. Yet, the function of this diversity, as well as the consequences of its loss, remains unknown. This review will bring together recent advances in HSC diversity and novel insights into myeloid heterogeneity and specification in order to bring focus on how this may affect the ageing individual.
Recent findings
The ageing haematopoietic system is dominated by a low number of ac...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research
Emerging single-cell tools are primed to reveal functional and molecular heterogeneity in malignant hematopoietic stem cells
Purpose of review
The recent emergence of single-cell technologies has permitted unprecedented insight into the molecular drivers of fate choice in blood stem and progenitor cells. This review gives a broad overview of current efforts to understand the molecular regulators of malignant hematopoietic stem cells (HSCs) at the single-cell level.
Recent findings
The large-scale adoption of single-cell approaches has allowed extensive description of the transcriptional profiles and functional properties of single HSCs. These techniques are now beginning to be applied to malignant HSCs isolated directly from patients or fro...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research
Toll-like receptor signaling in hematopoietic stem and progenitor cells
Purpose of review
The innate immune system is essential in the protection against microbial infection and facilitating tissue repair mechanisms. During these stresses, the maintenance of innate immune cell numbers through stress-induced or emergency hematopoiesis is key for our survival. One major mechanism to recognize danger signals is through the activation of Toll-like receptors (TLRs) on the surface of hematopoietic cells, including hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC), and nonhematopoietic cells, which recognize pathogen-derived or damaged-induced compounds and can influence the eme...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Emerging molecular mechanisms of vascular dementia
Purpose of review
Microvascular ischemic disease of the brain is a common cause of cognitive impairment and dementia, particularly in the context of preexisting cardiovascular risk factors and aging. This review summarizes our current understanding of the emerging molecular themes that underlie progressive and irreparable vascular disease leading to neuronal tissue injury and dementia.
Recent findings
Cardiometabolic risk factors including diabetes and hypertension are known to contribute to vascular disease. Currently, the impact of these risk factors on the integrity and function of the brain vasculature has been ta...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research
CADASIL: new advances in basic science and clinical perspectives
Purpose of review
Recent advances in genetic evaluation improved the identification of several variants in the NOTCH3 gene causing Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Despite improved diagnosis, the disease mechanism remains an elusive target and an increasing number of scientific/clinical groups are investigating CADASIL to better understand it. The purpose of this review is to summarize the current knowledge in CADASIL.
Recent findings
CADASIL is a genotypically and phenotypically diverse condition involving multiple molecular systems affecting small ...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research
Rapamycin and treatment of venous malformations
Purpose of review
The field of vascular anomalies has seen a fundamental change during the past 10 years. The identification of somatic genetic mutations as the explanation of sporadic vascular anomalies opened the doors to study prospectively and a posteriori the causes of various vascular malformations. This was helped by the rapidly evolving genetic techniques including the highly sensitive next generation sequencing. In parallel, knowledge on signaling alterations occurring in vascular endothelial cells because of the various mutations, development of in-vitro and especially the first in-vivo models, gave the possibi...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research
A somatic missense mutation in GNAQ causes capillary malformation
Purpose of review
Capillary malformations, the most common type of vascular malformation, are caused by a somatic mosaic mutation in GNAQ, which encodes the Gαq subunit of heterotrimeric G-proteins. How the single amino acid change – predicted to activate Gαq – causes capillary malformations is not known but recent advances are helping to unravel the mechanisms.
Recent findings
The GNAQ R183Q mutation is present not only in endothelial cells isolated from skin and brain capillary malformations but also in brain tissue underlying the capillary malformation, raising questions about the origin of capillary malforma...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research
PIK3CA mutations in vascular malformations
Purpose of review
Recently, it has been discovered that a subset of vascular malformations, of the lymphatic and venous type, are caused by oncogenic mutations in the PIK3CA gene. Now, efforts have been focused in the understanding of the molecular and cellular consequences of these mutations and the opportunities for novel-targeted therapies for these diseases.
Recent findings
Here, we review the latest findings in the biology of oncogenic PIK3CA mutations in the pathogenesis of vascular malformations. We focus on the recent development of in-vitro and in-vivo tools for the study of PIK3CA-mutant vascular malformatio...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research
Deregulation of Drosha in the pathogenesis of hereditary hemorrhagic telangiectasia
Purpose of review
The TGFβ (transforming growth factor β) superfamily – a large group of structurally related and evolutionarily conserved proteins – profoundly shapes and organizes the vasculature during normal development and adult homeostasis. Mutations inactivating several of its ligands, receptors, or signal transducers set off hereditary hemorrhagic telangiectasia (HHT), a disorder that causes capillary networks to form incorrectly. Drosha, an essential microRNA-processing enzyme, also interfaces with TGFβ signal transducers, but its involvement in vascular conditions had not been tested until recently. This...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research
Bone morphogenetic protein and blood vessels: new insights into endothelial cell junction regulation
Purpose of review
BMP signaling is an important regulator of vascular development and homeostasis, and perturbations of BMP pathway components are linked to vascular disease. However, until recently BMP's broad requirements in many developmental programs delayed cause-and-effect and mechanistic studies of its vascular role in vivo. This review covers recent findings that illuminate the role of BMP signaling in endothelial cells of blood vessels, and highlights effects of BMP signaling on endothelial cell junctions and vascular barrier function.
Recent findings
BMP signaling in endothelial cells of blood vessels is con...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research
A focus on vascular malformations
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research
Oxidation and erythropoiesis
Purpose of review
Erythropoiesis is a complex multistep process going from committed erythroid progenitors to mature red cells. Although recent advances allow the characterization of some components of erythropoiesis, much still remains to be investigated particularly on stress erythropoiesis. This review summarizes recent progresses made to understand the impact of oxidative stress on normal and pathologic erythropoiesis.
Recent findings
During erythroid maturation, reactive oxygen species might function as second messenger through either transient oxidation of cysteine residues on signaling targets or modulation of ...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research
