Reticular dysgenesis–associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress

Rissone, Alberto; Weinacht, Katja G.; Marca, Giancarlo la; Bishop, Kevin; Giocaliere, Elisa; Jagadeesh, Jaya; Felgentreff, Kerstin; Dobbs, Kerry; Al‐Herz, Waleed; Jones, MaryPat; Chandrasekharappa, Settara C.; Kirby, Martha; Wincovitch, Stephen; Simon, Karen L.; Itan, Yuval; DeVine, Alexander L.; Schlaeger, Thorsten M.; Schambach, Axel; Sood, Raman; Notarangelo, Luigi D.; Candotti, Fabio

doi:10.1083/jcb.2102oia141

Cited by 11 publications

(23 citation statements)

References 43 publications

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“…An initial model of morpholino oligonucleotide (MO)–mediated knockdown of zebrafish ( Danio rerio ) ak2 expression does not affect the overall development of embryos but the morphants exhibited defects in leucocyte development with absent T cells in the thymus anlage (Pannicke et al , ). In a refinement of the zebrafish studies, ak2 mutant lines showed a profound impairment of lymphoid as well as myeloid cell development (Rissone et al , ). Additionally, a markedly reduced expression of the erythroid marker hbae1.1 was noted, supporting the idea that erythropoiesis defects are intrinsic to Ak2 deficiency in this model.…”

Section: Pathophysiology Of Ak2 Deficiency In Cellular and Animal Modelsmentioning

confidence: 99%

“…The observation of a large fraction of anaemic RD patients at birth complements these observations (Hoenig et al , ). Furthermore, Rissone et al () showed that increased oxidative stress and reactive oxygen species (ROS) production results in cell death and apoptosis and that Ak2 deficiency causes a progressive reduction of haematopoietic stem and progenitor cells by this mechanism. These developmental blocks in the Ak2‐deficient zebrafish model could be reversed by antioxidative treatment.…”

Section: Pathophysiology Of Ak2 Deficiency In Cellular and Animal Modelsmentioning

confidence: 99%

“…This block is imitated in colony‐forming assays with bone marrow mononuclear cells originating from RD patients (Lagresle‐Peyrou et al , ). Red cell precursors derived of AK2 iPSC were dysplastic and erythroid colony building capacity was markedly reduced (Rissone et al , ). The myeloid differentiation block of AK2 patient‐derived iPSC was overcome by antioxidative treatment (Rissone et al , ).…”

Section: Pathophysiology Of Ak2 Deficiency In Cellular and Animal Modelsmentioning

confidence: 99%

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Recent advances in understanding the pathogenesis and management of reticular dysgenesis

et al. 2017

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Reticular Dysgenesis is a rare immunodeficiency which is clinically characterized by the combination of Severe Combined Immunodeficiency (SCID) with agranulocytosis and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 (AK2) were identified to cause this phenotype. In this review, we will demonstrate important clinical differences between reticular dysgenesis and other SCID entities and summarize recent concepts in the understanding of the pathophysiology of the disease and the management strategies for this difficult condition.

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Section: Pathophysiology Of Ak2 Deficiency In Cellular and Animal Modelsmentioning

confidence: 99%

Section: Pathophysiology Of Ak2 Deficiency In Cellular and Animal Modelsmentioning

confidence: 99%

Section: Pathophysiology Of Ak2 Deficiency In Cellular and Animal Modelsmentioning

confidence: 99%

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Recent advances in understanding the pathogenesis and management of reticular dysgenesis

et al. 2017

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“…Intracellular reactive oxygen species (ROS) are a byproduct of mitochondrial oxidative phosphorylation that are generated by the respiratory chain primarily in the form of superoxide anions (O 2 − ) and are immediately transformed by mitochondrial superoxide dismutase (MnSOD) to hydrogen peroxide (H 2 O 2 ) (5). HSPCs are highly sensitive to ROS and under normal physiological condition; ROS levels are tightly regulated to prevent hematopoietic cell damage (6)(7)(8). Accumulating evidence indicates that the inability to regulate high levels of ROS can lead to impaired stem and progenitor cell homeostasis and bone marrow failure (6)(7)(8)(9).…”

mentioning

confidence: 99%

“…HSPCs are highly sensitive to ROS and under normal physiological condition; ROS levels are tightly regulated to prevent hematopoietic cell damage (6)(7)(8). Accumulating evidence indicates that the inability to regulate high levels of ROS can lead to impaired stem and progenitor cell homeostasis and bone marrow failure (6)(7)(8)(9). Evidence also suggest a role for chronic oxidative stress in the progression of radiation-induced acute and late hematopoietic syndromes (10,11), stem cell aging and (12) degenerative diseases (13), whereas ROS scavengers improve HSPC function and engraftment (9,14).…”

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confidence: 99%

IFN-1 Bid crosstalk: foe or friend to stem cells

Singh

Pelus

2017

Stem Cell Investig.

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Genome‐Wide Analysis of DNA Methylation and Antituberculosis Drug‐Induced Liver Injury in the Han Chinese Population

Cong

Wei

et al. 2019

Clin Pharma and Therapeutics

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Tuberculosis (TB) is one of the most prevalent infections. However, anti-TB drugs induce adverse liver injury in up to 40% of patients. Studies on candidate genes have suggested that single-nucleotide polymorphisms account for only a small contribution to the occurrence of anti-TB drug-induced liver injury (ATLI). In this study, whole-genome DNA methylation analysis was performed to systematically screen the ATLI-associated factors in a 49 vs. 51 case-control population. Next, 34 identified candidate probes were validated using MassARRAY in 296 cases and 288 controls. Our results indicated that 12 CpG sites on seven probes were positively associated with ATLI risk. Furthermore, we applied a CRISPR/Cas9-mediated methylation modifiable cell model and demonstrated that four CpGs in or near the gene region of AK2, SLC8A2, and PSTPIP2 affected the cellular response to rifampicin treatment. This study provides new biomarkers associated with ATLI occurrence.Tuberculosis (TB) is one of the most prevalent chronic bacterial infections, with >6 million new cases occurring globally each year. 1 Although the first-line therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol is able to suppress the increasing incidence of TB, 1 it has been reported that ~ 0.8-40% of patients worldwide suffer from anti-TB drug-induced liver injury (ATLI). 2 ATLI is the most common side effect of anti-TB drugs and often leads to the delayed completion or failure of chemotherapy in patients. 3,4 In some extreme cases, ATLI causes irreversible hepatonecrosis or death in patients receiving anti-TB treatment.Recently, the mortality rate of ATLI was estimated to be as high as 22.7%. 2 Therefore, ATLI is regarded as a severe clinical problem that poses a significant challenge to the early control of TB progression.Numerous association studies have attempted to identify the risk factors for ATLI. A number of genetic single-nucleotide polymorphisms (SNPs) in various genes have been reported to be related to the development of ATLI. The majority of these identified genes are involved in the pathways of drug absorption, distribution, metabolism, and excretion (ADME), acquired immunity, innate immune

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Reticular dysgenesis–associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress

Cited by 11 publications

References 43 publications

Recent advances in understanding the pathogenesis and management of reticular dysgenesis

Recent advances in understanding the pathogenesis and management of reticular dysgenesis

IFN-1 Bid crosstalk: foe or friend to stem cells

Genome‐Wide Analysis of DNA Methylation and Antituberculosis Drug‐Induced Liver Injury in the Han Chinese Population

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