Luspatercept for the treatment of β-thalassemia: from preclinical research to clinical practice and beyond

β-thalassemia is an inherited disease causing an impaired hemoglobin production, eventually leading to a severe chronic anemia. Resolutive treatments are still limited to a small number of patients and blood transfusions still represent the standard of care. In this scenario, luspatercept is the first approved drug able to significantly modify the disease phenotype. Developed as a fusion protein, it binds TGF-β ligands, contributing to a reduction of ineffective erythropoiesis. As shown by clinical trials in thalassemia, this effect determines an increase in mean hemoglobin levels and/or a decrease in transfusion burden. While some potential indications are still being evaluated in trials, luspatercept has recently entered the clinical practice for transfusion-dependent thalassemia patients.

Hemogen/BRG1 Cooperativity Is Required for Erythrocyte Maturation and Hemoglobin Production during Mammalian Erythropoiesis

Hemogen, also known as EDAG, is a hematopoietic tissue-specific gene that regulates the proliferation and differentiation of hematopoietic cells. However, the mechanism underlying hemogen function in erythropoiesis is unclear. We found that depletion of hemogen in human CD34 + erythroid progenitor cells and HUDEP2 cells significantly reduced the expression of genes associated with heme and hemoglobin synthesis, supporting a positive role of hemogen in erythroid maturation. In human K562 cells, hemogen antagonized the occupancy of co-repressors NuRD complex and facilitated LDB1 complex-mediated chromatin looping. Hemogen recruited SWI/SNF complex ATPase BRG1 as a co-activator to regulate nucleosome accessibility and H3K27ac enrichment for promoter and enhancer activity. To ask if hemogen/BRG1 cooperativity is conserved in mammalian systems, we generated hemogen KO/KI mice and investigated hemogen/BRG1 function in murine erythropoiesis. Loss of hemogen in E12.5-E16.5 impeded erythroid differentiation through reducing the production of mature erythroblasts. ChIP-seq in WT and hemogen KO animal revealed BRG1 is largely dependent on hemogen to occupy chromatin at erythroid gene promoters and enhancers. In summary, hemogen/BRG1 interaction in mammals is essential for erythroid maturation and hemoglobin production through its active role in promoter and enhancer activity and chromatin organization. Disclosures No relevant conflicts of interest to declare.

Beta Thalassemia Major with Diabetes Mellitus: A Case Report

Thalassemia results from defects in normal hemoglobin production, and represents the most common inherited anemia worldwide. Diabetes is a complication of b-thalassemia major. We report a case of Diabetes mellitus in a known case of beta thalassemia major. Patient had undergone Splenectomy 1 year back. Patient is taking chelating agent Defasirox 1000mg orally once a day in the morning. Family history reveals, born through third degree consanguineous marri age. The patient was then subjected for laboratory examination reveals BSL was high, urine ketone 2+,urine sugar 3+, ABG was normal, HbA1c was 13 & 3 month old report of serum ferritin 1200 ng/dl. Multidisciplinary management was instituted. Blood sugar level got controlled over subcutaneous insulin. Patient may have landed in Diabetic ketoacidosis but was promptly diagnosed & treated. This case is presented for its rarity. As the life expectancy of patients with thalassaemia increases, this will also expose our patients potentially to many more years of hyperglycaemia and diabetes. Sustaining metabolic control and controlling cardiovascular risk factors will be critical in the future for preventing complications due to diabetes.

A STUDY TO FIND THE DISTRIBUTION OF ABO BLOOD GROUP IN BETA THALASSEMIA

INTRODUCTION: - Beta thalassemia (ẞ-thalassemia) is an inherited hematological disorder involving decreased amount of hemoglobin production. It is a major problem of concern causing high mortality rates in children. Thalassemia patients suffer from severe anemia due to which they need to get repeated blood transfusion after a regular period of time. Many studies have reported association of ABO blood group with diseases. AIM AND OBJECTIVES: - To study the relation between the ABO blood group and beta thalassemia. MATERIALS AND METHODS: - This was a cross sectional, observational survey-based on study conducted at Dept. of Physiology, A’bad with the help of Thalassemia Care Centre, Civil Hospital, Ahmedabad. The study was conducted on 300 registered beta thalassemia major patients during February 2019 to August 2019 over a period of 6 months. These patients visited the thalassemia care center for repeated blood transfusion. Blood group of the patient was determined by Slide Agglutination Method at Department of Physiology. Results were prepared & tabulated in Microsoft Excel 2013. RESULTS: - It is found that among the study that males were more affected than females. It is more prevalent in Rh positive individuals as compared to Rh negative. Frequency of blood groups affecting patients were O>B>A>AB. CONCLUSION: - Thalassemia is more prevalent in males than females. The most commonly affected blood group is O positive followed by B positive, A positive and last AB positive. Among the Rh blood group, Rh positive were more as compared to Rh negative but Rh-negative females were more common than Rh positive males.