Sickle cell disease (SCD) is a single gene genetic disease, which seriously threatens the life span and quality of patients. On the basis of the pathogenesis of SCD and the alternative therapy based on fetal hemoglobin F (HbF), the research progress of transcription factors involved in the regulation of HbF gene expression, such as BCL11A, ZBTB7A, KLF-1, c-MYB and SOX6, as well as the application of CRISPR / Cas9, TALEN, zinc finger nuclease and other gene editing technologies in this field has been made, providing a solid theoretical basis for the exploration of new treatment schemes for β- like hemoglobin diseases, such as sickle cell disease and β- thalassemia.
Anemia, Sickle Cell/therapy* ; Cell Line, Tumor ; DNA-Binding Proteins ; Fetal Hemoglobin/genetics* ; Genetic Therapy ; Humans ; Repressor Proteins/genetics* ; Transcription Factors

Hereditary hemolytic anemia is a very heterogeneous disorder in which abnormalities of red blood cell structural protein, globin protein, or enzyme defect lead to shortened life span. There has been much progress in revealing its pathophysiology and genetic backgrounds, but the lifelong plans for caring these patients are not well established yet. All patients with hereditary hemolytic anemic have three common problems: transfusion dependency, iron overload and iron chelation therapy. Patients with hereditary spherocytosis (HS) usually manifest severe anemia in neonatal period and infancy, but transfusion requirements may decrease in adulthood. But patients with thalassemia or sickle cell disease usually transfusion-dependent throughout life. Maintaining the optimal hemoglobin (Hb) levels in these patients is crucial because correction of anemia and dilution of abnormal Hb helps prevent certain complications that frequently occur in these patients. Frequent transfusion leads to transfusion-mediated infection and hemochromatosis. Iron chelation therapy should be started early to prevent permanent organ damage. Folate therapy can be helpful in patients with hereditary spherocytosis. Regular evaluations for cholestasis should be started at age 5, and splenectomy with concurrent cholecystectomy can be considered if the patient has cholecystitis. Hydroxyurea can be used to reduce transfusion requirements and prevent complications in patients with β-thalassemia and sickle cell disease. Consensus on long-term management of patients with hereditary hemolytic anemia is lacking, especially for adult patients. But further efforts to build guidelines for long-term follow-up and management of the patients with hereditary hemolytic anemia in the context of Korean society are needed.
Adult ; Anemia ; Anemia, Hemolytic, Congenital ; Anemia, Sickle Cell ; Chelation Therapy ; Cholecystectomy ; Cholecystitis ; Cholestasis ; Consensus ; Erythrocytes ; Folic Acid ; Follow-Up Studies ; Globins ; Hemochromatosis ; Humans ; Hydroxyurea ; Iron ; Iron Overload ; Splenectomy ; Thalassemia

Sickle cell disease and beta-thalassemia are caused by abnormal hemoglobin (Hb) derived from mutation of the HBB gene encoding beta-globin. Compound heterozygous status for both mutations results in Hb S/beta-thalassemia (sickle-beta-thalassemia). Vaso-occlusive phenomena and hemolysis are the clinical hallmarks and major causes of mortality. Due to the limited availability of hematopoietic stem cell transplantation with or without gene therapy, red blood cell (RBC) exchange transfusion is the first-line adjunctive therapy. Here we report on a successful reduction of Hb S level in a Tunisian male sickle-beta-thalassemia patient by RBC exchange transfusion for primary prophylactic transfusion therapy before flying to his country. Results of both Ion exchange high-performance liquid chromatography and HBB gene mutation analysis indicated sickle-beta-thalassemia. Pre-erythrocytapheresis Hb S level was 80.6% of total Hb. Two volumes of RBC exchange were performed using automated erythrocytapheresis with the COBE Spectra Apheresis System (Version 7.0, Caridian BCT, CO, USA). Post-erythrocytapheresis Hb S level was 23.4% of total Hb and hematocrit level was 32.6%, both of which met the target end points. This is the first case report in Korea on successful RBC exchange transfusion in a patient with sickle-beta-thalassemia for rapid reduction of pathologic RBCs with Hb S.
Anemia, Sickle Cell ; beta-Globins ; beta-Thalassemia ; Blood Component Removal ; Blood Transfusion ; Chromatography, Liquid ; Diptera ; Erythrocytes ; Genetic Therapy ; Hematocrit ; Hematopoietic Stem Cell Transplantation ; Hemoglobins ; Hemolysis ; Humans ; Ion Exchange ; Korea ; Male ; Thalassemia

Sickle cell disease and beta-thalassemia are caused by abnormal hemoglobin (Hb) derived from mutation of the HBB gene encoding beta-globin. Compound heterozygous status for both mutations results in Hb S/beta-thalassemia (sickle-beta-thalassemia). Vaso-occlusive phenomena and hemolysis are the clinical hallmarks and major causes of mortality. Due to the limited availability of hematopoietic stem cell transplantation with or without gene therapy, red blood cell (RBC) exchange transfusion is the first-line adjunctive therapy. Here we report on a successful reduction of Hb S level in a Tunisian male sickle-beta-thalassemia patient by RBC exchange transfusion for primary prophylactic transfusion therapy before flying to his country. Results of both Ion exchange high-performance liquid chromatography and HBB gene mutation analysis indicated sickle-beta-thalassemia. Pre-erythrocytapheresis Hb S level was 80.6% of total Hb. Two volumes of RBC exchange were performed using automated erythrocytapheresis with the COBE Spectra Apheresis System (Version 7.0, Caridian BCT, CO, USA). Post-erythrocytapheresis Hb S level was 23.4% of total Hb and hematocrit level was 32.6%, both of which met the target end points. This is the first case report in Korea on successful RBC exchange transfusion in a patient with sickle-beta-thalassemia for rapid reduction of pathologic RBCs with Hb S.
Anemia, Sickle Cell ; beta-Globins ; beta-Thalassemia ; Blood Component Removal ; Blood Transfusion ; Chromatography, Liquid ; Diptera ; Erythrocytes ; Genetic Therapy ; Hematocrit ; Hematopoietic Stem Cell Transplantation ; Hemoglobins ; Hemolysis ; Humans ; Ion Exchange ; Korea ; Male ; Thalassemia

OBJECTIVETo investigate the effects of combined use of low-dose hydroxyurea (HU) and sodium butyrate (NaB) on the expression of 7 globin genes (zeta, alpha, epsilon, Ggamma, Agamma, delta, and beta) in human erythroid progenitor cells.

METHODSHuman erythroid progenitor cells were cultured using a two-step liquid culture system and treated with HU and NaB either alone or in combination. The inhibitory effects of the agents on the cell growth were monitored with trypan blue exclusion assay, and the changes in the mRNA of the 7 globin genes were detected using RT-PCR.

RESULTSLow-dose HU combined with NaB resulted in significantly lower inhibition rate of the erythroid progenitor cells than routine dose HU and NaB used alone (28.56% and 38.80%, respectively, P<0.05). Compared with untreated cells (0.653-/+0.092 and 0.515-/+0.048), HU combined with NaB significantly increased the expression of Ggamma-and Agamma- mRNA (1.203-/+0.018 and 0.915-/+0.088, respectively, P<0.05), and HU and NaB used alone produced similar effects (1.305-/+0.016 and 0.956-/+0.029 for HU, and 1.193-/+0.070 and 0.883-/+0.012 for NaB, P>0.05). HU and NaB, either used alone or in combination or at different doses, caused no significant changes in the other globin genes (zeta, alpha, epsilon, delta and beta) (P>0.05).

CONCLUSIONLow-dose HU combined with NaB can up-regulate gamma globin gene expression, especially Ggamma-mRNA expression, to decrease the growth inhibition on human erythroid progenitor cells in vitro, but produces no significant effect on the expressions of zeta, alpha, epsilon, delta and beta genes.

Anemia, Sickle Cell ; genetics ; Butyrates ; administration & dosage ; pharmacology ; therapeutic use ; Cells, Cultured ; Drug Therapy, Combination ; Erythroid Precursor Cells ; cytology ; drug effects ; physiology ; Erythropoiesis ; drug effects ; Humans ; Hydroxyurea ; administration & dosage ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; gamma-Globins ; genetics ; metabolism