Clinical and Haematological Effects of Hydroxyurea in β -Thalassemia Intermedia Patients

Keikhaei, Bijan; Yousefi, Homayon; Bahadoram, Mohammad

doi:10.7860/jcdr/2015/14807.6660

Cited by 13 publications

(9 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, SPR-BIA has been extensively used in studies focused on the effects of low molecular weight drugs able to interfere with protein-DNA interaction. These studies would be relevant for the design of therapeutic protocols for β-thalassemia, since increase of HbF production has been firmly demonstrated to reduce the clinical severity of β-thalassemia [7,8]. Furthermore, our study strongly supports the interest in determining the rs368698783 G>A polymorphism in β-thalassemia patients and in verifying possible use to predict HbF production as well as response to HbF inducers.…”

Section: Discussionsupporting

confidence: 68%

“…At present, the only treatment that can be considered a cure for β-thalassemia is transplantation of hematopoietic stem cells (bone marrow transplantation) [5]. Alternatively, growing evidence supports the concept that induction of γ-globin gene expression and increased production of fetal hemoglobin (HbF) might be of great interest for the development of therapeutic protocols for β-thalassemia [6][7][8][9], possibly obviating the need for blood transfusions in β-thalassemia patients [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Surface plasmon resonance based analysis of the binding of LYAR protein to the rs368698783 (G>A) polymorphic Aγ-globin gene sequences mutated in β-thalassemia

et al. 2019

View full text Add to dashboard Cite

Recent studies have identified and characterized a novel putative transcriptional repressor site in a 5′ untranslated region of the Aγ-globin gene that interacts with the Ly-1 antibody reactive clone (LYAR) protein. LYAR binds the 5'-GGTTAT-3' site of the Aγ-globin gene, and this molecular interaction causes repression of gene transcription. In β-thalassemia patients, a polymorphism has been demonstrated (the rs368698783 G>A polymorphism) within the 5′-GGTTAT-3′ LYAR-binding site of the Aγ-globin gene. The major results gathered from surface plasmon resonance based biospecific interaction analysis (SPR-BIA) studies (using crude nuclear extracts, LYAR-enriched lysates, and recombinant LYAR) support the concept that the rs368698783 G>A polymorphism of the Aγ-globin gene attenuates the efficiency of LYAR binding to the LYAR-binding site. This conclusion was fully confirmed by a molecular docking analysis. This might lead to a very important difference in erythroid cells from β-thalassemia patients in respect to basal and induced levels of production of fetal hemoglobin. The novelty of the reported SPR-BIA method is that it allows the characterization and validation of the altered binding of a key nuclear factor (LYAR) to mutated LYAR-binding sites. These results, in addition to theoretical implications, should be considered of interest in applied pharmacology studies as a basis for the screening of drugs able to inhibit LYAR-DNA interactions. This might lead to the identification of molecules facilitating induced increase of γ-globin gene expression and fetal hemoglobin production in erythroid cells, which is associated with possible reduction of the clinical severity of the β-thalassemia phenotype.

show abstract

Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Surface plasmon resonance based analysis of the binding of LYAR protein to the rs368698783 (G>A) polymorphic Aγ-globin gene sequences mutated in β-thalassemia

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Another study supported the functionality of the prevention program (4). In addition, some studies have reported a significant improvement in treatment (5) and the quality of life in patients (6), decreasing mortality (7), and improving the survival rate (8). Notwithstanding the mentioned issues, it is estimated that over 300 new cases are born every year (9).…”

Section: Introductionmentioning

confidence: 78%

Delay in Diagnosis of Hemoglobulinopathies (Thalassemia, Sickle Cell Anemia): A Need for Management of Thalassemia Programs

et al. 2016

View full text Add to dashboard Cite

Background: Hemoglobulinopathies (Thalassemia, Sickle cell anemia) are an important public health challenge worldwide with an estimated number of 330,000 affected newborns annually. Delay in diagnosis not only increases the morbidity and mortality rates, but also can lead to uncertainties about success of thalassemia prevention program (TPP). This study is the first to determine the delay in thalassemia diagnosis in Iranian population. Methods: This registry-based cross-sectional study was conducted on 1003 enrolled thalassemic patients in 2015 in Shiraz, Iran. Univariate and multivariate ordinal logistic regression models were used to assess the factors associated with delay in diagnosis. Results: Of 981 patients, 48.5% were female, 71.2% were thalassemia major, and 23.8% were death cases. The delay in diagnosis was observed among 64.9% of the patients with a mean of 13.4 months (95% CI: 10.9, 15.9). Multivariate ordinal logistic regression showed that girls (adjusted OR = 1.32), and dead patients (adjusted OR = 1.95) were more likely to have delayed diagnosis. There was an increasing trend of risk in delayed diagnosis associated with one-year per birth cohort. The ORs were 1.0, 1.52, 1.55, and 2.22, for birth cohort 1980 and earlier, 1981 -1990, 1991 -2000, and 2001 to the present, respectively (P for trend = 0.014). In addition, the odds of delayed diagnosis in thalassemia major patients were significantly 0.58 times lower than those with thalassemia intermedia. Conclusions: A high proportion of delayed diagnosis was found. These results could explain the poor outcomes for thalassemia patients. Educational programs for community and revising the TPP are required for early detection of the disease.

show abstract

“…Thalidomide, a drug known for immunomodulating and anti‐angiogenic properties, has been shown to induce γ‐globin gene expression and increase the proliferation of erythroid cells (Gambari, ), which could be through the amplification of reactive oxygen species (ROS)‐p38 mitogen‐activated protein kinase (MAPK) signalling and histone H4 acetylation during adult erythropoiesis (Aerbajinai et al , ). Furthermore, hydroxyurea (HU) is known to increase haemoglobin (Hb) by HbF induction and reduction of inflammation and hypercoagulability (Keikhaei et al , ).…”

Section: Clinical Characteristics Change Of Hb (G/l) and Transfusionmentioning

confidence: 99%

Safety and effectiveness of thalidomide and hydroxyurea combination in β‐thalassaemia intermedia and major: a retrospective pilot study

et al. 2019

View full text Add to dashboard Cite

Clinical and Haematological Effects of Hydroxyurea in β -Thalassemia Intermedia Patients

Cited by 13 publications

References 10 publications

Surface plasmon resonance based analysis of the binding of LYAR protein to the rs368698783 (G>A) polymorphic Aγ-globin gene sequences mutated in β-thalassemia

Surface plasmon resonance based analysis of the binding of LYAR protein to the rs368698783 (G>A) polymorphic Aγ-globin gene sequences mutated in β-thalassemia

Delay in Diagnosis of Hemoglobulinopathies (Thalassemia, Sickle Cell Anemia): A Need for Management of Thalassemia Programs

Safety and effectiveness of thalidomide and hydroxyurea combination in β‐thalassaemia intermedia and major: a retrospective pilot study

Contact Info

Product

Resources

About