The past three decades have witnessed an explosion in information regarding the genetic mutations underlying predisposition to common malignancies. Discoveries are now being made regarding genomic variants associated with disease…
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…
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…
Although inherited predisposition to colorectal cancer (CRC) has been suspected for more than 100 years, definitive proof of Mendelian syndromes had to await maturation of molecular genetic technologies. Since the…
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…
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%…
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…
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…
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…
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…
