Association of Xmn

Background and Objectives. To explore the role of cis-regulatory sequences within the β globin gene cluster at chromosome 11 on human γ globin gene expression related to Hb E allele, we analyze baseline hematological data and Hb F values together with β globin haplotypes in homozygous Hb E. Patients and Methods. 80 individuals with molecularly confirmed homozygous Hb E were analyzed for the β globin haplotypes and Xmn I polymorphism using PCR-RFLPs. 74 individuals with complete laboratory data were further studied for association analyses. Results. Eight different β globin haplotypes were found linked to Hb E alleles; three major haplotypes were (a) (III), (b) (V), and (c) (IV) accounting for 94% of Hb E chromosomes. A new haplotype (Th-1) was identified and most likely converted from the major ones. The majority of individuals had Hb F < 5%; only 10.8% of homozygous Hb E had high Hb F (average 10.5%, range 5.8–14.3%). No association was found on a specific haplotype or Xmn I in these individuals with high Hb F, measured by alkaline denaturation. Conclusion. The cis-regulation of γ globin gene expression might not be apparent under a milder condition with lesser globin imbalance such as homozygous Hb E

Recent advances in molecular understanding of NTDT: 2012

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The regulation of #alpha# and #beta# globin gene expression

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Iron Chelation Therapy in the Management of Thalassemia: The Asian Perspectives

Worldwide, thalassemia is the most commonly inherited hemolytic anemia, and it is most prevalent in Asia and the Middle East. Iron overload represents a significant problem in patients with transfusion-dependent beta-thalassemia. Chelation therapy with deferoxamine has traditionally been the standard therapeutic option but its usage is tempered by suboptimal patient compliance due to the discomfort and demands associated with the administration regimen. Therefore, a great deal of attention has been focused on the development of oral chelating agents. Deferiprone, even though available for nearly two decades in Asia with recent encouraging data on cardiac iron removal and long-term efficacy, has serious adverse effects including agranulocytosis and neutropenia which has impeded it from routine clinical practice. A novel oral chelator; deferasirox is effective throughout a 24 h dosing period and both preclinical and clinical data indicate that it successfully removes both hepatic and cardiac iron. In Asia, optimal management of severe thalassemia patients and the availability and access to oral iron chelators still presents a major challenge in many countries. In this regard , the development and implementation of consensus guidelines for management of Asian patients with transfusion-dependent thalassemia will be a major step towards improving and maintaining the continuity of patient care

Clinical Efficacy and Safety Evaluation of Tailoring Iron Chelation Practice in Thalassaemia Patients from Asia-Pacific: A Subanalysis of the Epic Study of Deferasirox

Although thalassaemia is highly prevalent in the Asia- Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients' Iron Chelation with Exjade EPIC study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia- Pacific region AP for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world ROW, baseline clinical data showed that the AP group appeared to be more loaded with iron 3745.0 vs. 2822.0 ng/ml and had a higher proportion on deferoxamine monotherapy prior to the study 82.9 vs. 58.9%. Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW 18.0 vs. 7.2%, which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects

Current approach to iron chelation in children

WOS: 000337520600003PubMed ID: 24646011Transfusion-dependent children, mostly with thalassaemia major, but also and occasionally to a more significant degree, with inherited bone marrow failures, can develop severe iron overload in early life. Moreover, chronic conditions associated with ineffective erythropoiesis, such as non-transfusion-dependent thalassaemia (NTDT), may lead to iron overload through increased gut absorption of iron starting in childhood. Currently, the goal of iron chelation has shifted from treating iron overload to preventing iron accumulation and iron-induced end-organ complications, in order to achieve a normal pattern of complication-free survival and of quality of life. New chelation options increase the likelihood of achieving these goals. Timely initiation, close monitoring and continuous adjustment are the cornerstones of optimal chelation therapy in children, who have a higher transfusional requirements compared to adults in order to reach haemoglobin levels adequate for normal growth and development. Despite increased knowledge, there are still uncertainties about the level of body iron at which iron chelation therapy should be started and about the appropriate degree of iron stores' depletion.Shire; Shire and Novartis; Government Pharmaceutical Organization (GPO), ThailandYA has received research funding from Shire and Novartis; consultancy from Novartis and is a member of the speaker bureau for Novartis. AK has received research funding from Novartis and is a member of the speaker bureau for Novartis and ApoPharma. V.V. has received research funding from The Government Pharmaceutical Organization (GPO), Thailand, Shire and Novartis; consultancy from Shire and Novartis and is a member of the speaker bureau for Novartis

Current approach to iron chelation in children

Transfusion-dependent children, mostly with thalassaemia major, but also and occasionally to a more significant degree, with inherited bone marrow failures, can develop severe iron overload in early life. Moreover, chronic conditions associated with ineffective erythropoiesis, such as non-transfusion-dependent thalassaemia (NTDT), may lead to iron overload through increased gut absorption of iron starting in childhood. Currently, the goal of iron chelation has shifted from treating iron overload to preventing iron accumulation and iron-induced end-organ complications, in order to achieve a normal pattern of complication-free survival and of quality of life. New chelation options increase the likelihood of achieving these goals. Timely initiation, close monitoring and continuous adjustment are the cornerstones of optimal chelation therapy in children, who have a higher transfusional requirements compared to adults in order to reach haemoglobin levels adequate for normal growth and development. Despite increased knowledge, there are still uncertainties about the level of body iron at which iron chelation therapy should be started and about the appropriate degree of iron stores’ depletion