Mouse Models of Inherited Cancer Syndromes
Animal models of cancer have been instrumental in understanding the progression and therapy of hereditary cancer syndromes. The ability to alter the genome of an individual mouse cell in both…
Hemoglobin Gene Therapy for β-Thalassemia
Allogeneic stem cell transplantation currently is the only curative option for severe β-thalassemia and sickle cell disease. Human globin gene therapy with autotransplantation of transduced human hematopoietic stem cells is…
Noninvasive Approaches to Prenatal Diagnosis of Hemoglobinopathies Using Fetal DNA in Maternal Plasma
Fetal DNA is present in the plasma of pregnant women and can be used for noninvasive prenatal diagnosis. Early work had focused on the detection of paternally inherited fetal mutations…
Umbilical Cord Blood Transplantation for Thalassemia Major
Hematopoietic cell transplantation is curative therapy for thalassemia major. Although the clinical application of hematopoietic cell transplantation has relied on marrow collected from related and unrelated donors as the primary…
Allogeneic Cellular Gene Therapy for Hemoglobinopathies
Hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for patients with thalassemia major and sickle cell disease (SCD). Current myeloablative treatment protocols allow the cure of 78% to 90%…
Pharmacologic Induction of Fetal Hemoglobin Production
Reactivation of fetal hemoglobin (HbF) expression is an important therapeutic option in adult patients with hemoglobin disorders. The understanding of the developmental regulation of γ-globin gene expression was followed by…
Iron Overload in Thalassemia and Related Conditions: Therapeutic Goals and Assessment of Response to Chelation Therapies
Transfusional iron loading inevitably results in hepatic iron accumulation, with variable extrahepatic distribution that is typically less pronounced in sickle cell disease than in thalassemia disorders. Iron chelation therapy has…
Anemia, Ineffective Erythropoiesis, and Hepcidin: Interacting Factors in Abnormal Iron Metabolism Leading to Iron Overload in β-Thalassemia
β-Thalassemia is a genetic disorder caused by mutations in the β-globin gene and characterized by chronic anemia caused by ineffective erythropoiesis, and accompanied by a variety of serious secondary complications…
Protein Quality Control During Erythropoiesis and Hemoglobin Synthesis
Erythrocytes must regulate hemoglobin synthesis to limit the toxicities of unstable free globin chain subunits. This regulation is particularly relevant in β-thalassemia, in which β-globin deficiency causes accumulation of free…
HbE/β-Thalassemia: Basis of Marked Clinical Diversity
Hemoglobin E thalassemia accounts for about one-half of all cases of severe beta thalassemia. There is marked variability in its clinical severity ranging from an asymptomatic to a transfusion-dependent phenotype….
