Fetal hemoglobin regulation in β-thalassemia: heterogeneity, modifiers and therapeutic approaches

Sripichai, Orapan; Fucharoen, Suthat

doi:10.1080/17474086.2016.1255142

Cited by 46 publications

(43 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings have motivated the research of Hb switching, and pharmacological and molecular approaches to reactivate the expression of the γ-globin genes and the production of HbF [63]. Primary erythroid cultures recapitulate the pattern of Hb production in vivo [64]-cultures derived from embryonic or fetal sources produce mainly the embryonic (Gower 1 and 2) and fetal Hbs, while cultures derived from adult sources produce mainly HbA.…”

Section: Stimulation Of Hbf Productionmentioning

confidence: 99%

“…The research of other, more innocent and effective, drugs continues. New agents include those that affect chromatin regulators, such as decitabine on DNA methylation and histone deacetylase inhibitors and others that affect DNA-binding transcription factors [63].…”

Section: Stimulation Of Hbf Productionmentioning

confidence: 99%

“…This is most probably not a health issue since individuals with hereditary persistence of fetal hemoglobin that have high HbF (as high as 100%) are largely asymptomatic [94]. Moreover, as discussed above, in patients with β-hemoglobinopathies, including β-thal, high HbF ameliorates the symptoms (for review see [63]. In principle, high HbF-containing cRBC produced from the patient's PB progenitors or by the iPS technology from various somatic cells could be used for autologous transfusion.…”

Section: Production Of Rbc For Transfusionmentioning

confidence: 99%

See 2 more Smart Citations

Erythropoiesis In Vitro—A Research and Therapeutic Tool in Thalassemia

Fibach

2019

JCM

View full text Add to dashboard Cite

Thalassemia (thal) is a hereditary chronic hemolytic anemia due to a partial or complete deficiency in the production of globin chains, in most cases, α or β, which compose, together with the iron-containing porphyrins (hemes), the hemoglobin molecules in red blood cells (RBC). The major clinical symptom of β-thal is severe chronic anemia—a decrease in RBC number and their hemoglobin content. In spite of the improvement in therapy, thal still severely affects the quality of life of the patients and their families and imposes a substantial financial burden on the community. These considerations position β-thal, among other hemoglobinopathies, as a major health and social problem that deserves increased efforts in research and its clinical application. These efforts are based on clinical studies, experiments in animal models and the use of erythroid cells grown in culture. The latter include immortal cell lines and cultures initiated by erythroid progenitor and stem cells derived from the blood and RBC producing (erythropoietic) sites of normal and thal donors, embryonic stem cells, and recently, "induced pluripotent stem cells" generated by manipulation of differentiated somatic cells. The present review summarizes the use of erythroid cultures, their technological aspects and their contribution to the research and its clinical application in thal. The former includes deciphering of the normal and pathological biology of the erythroid cell development, and the latter—their role in developing innovative therapeutics—drugs and methods of gene therapy, as well as providing an alternative source of RBC that may complement or substitute blood transfusions.

show abstract

Section: Stimulation Of Hbf Productionmentioning

confidence: 99%

Section: Stimulation Of Hbf Productionmentioning

confidence: 99%

Section: Production Of Rbc For Transfusionmentioning

confidence: 99%

See 1 more Smart Citation

Erythropoiesis In Vitro—A Research and Therapeutic Tool in Thalassemia

Fibach

2019

JCM

View full text Add to dashboard Cite

show abstract

“…These findings have motivated the research of the mechanisms of Hb switching as well as for pharmacological and gene modification modalities to reactivate the expression of the γ-globin genes and production of HbF 75 .…”

Section: Stimulation Of Hbf Productionmentioning

confidence: 99%

Pathophysiology and treatment of patients with beta-thalassemia – an update

Fibach

Rachmilewitz

2017

F1000Res

View full text Add to dashboard Cite

Thalassemia (thal) is an autosomal recessive, hereditary, chronic hemolytic anemia due to a partial or complete deficiency in the synthesis of α-globin chains (α-thal) or β-globin chains (β-thal) that compose the major adult hemoglobin (α 2β 2). It is caused by one or more mutations in the corresponding genes. The unpaired globin chains are unstable; they precipitate intracellularly, resulting in hemolysis, premature destruction of red blood cell [RBC] precursors in the bone marrow, and a short life-span of mature RBCs in the circulation. The state of anemia is treated by frequent RBC transfusions. This therapy results in the accumulation of iron (iron overload), a condition that is exacerbated by the breakdown products of hemoglobin (heme and iron) and the increased iron uptake for the chronic accelerated, but ineffective, RBC production. Iron catalyzes the generation of reactive oxygen species, which in excess are toxic, causing damage to vital organs such as the heart and liver and the endocrine system. Herein, we review recent findings regarding the pathophysiology underlying the major symptoms of β-thal and potential therapeutic modalities for the amelioration of its complications, as well as new modalities that may provide a cure for the disease.

show abstract

“…Several therapeutic modalities aimed at reducing the dyserythropoiesis in thalassemia are currently under research. For example, activin receptor-II trap ligands, JAK2 inhibitors, induction of the Hsp70 chaperone machinery, reducing α-globin synthesis, and stimulation of HbF production [11][12][13][14][15].…”

Section: Novel Therapeutic Modalitiesmentioning

confidence: 99%