The Experts below are selected from a list of 171 Experts worldwide ranked by ideXlab platform
Martin H. Steinberg - One of the best experts on this subject based on the ideXlab platform.
-
Modulation of Fetal Hemoglobin in sickle cell anemia.
Hemoglobin, 2020Co-Authors: Martin H. SteinbergAbstract:A partial understanding of the pathophysiology of sickle cell disease has suggested one means of treatment—increasing the distribution and concentration of Fetal Hemoglobin in sickle erythrocytes. Although this can be accomplished clinically with drugs like hydroxyurea, a complete understanding of the molecular and cellular basis of Fetal Hemoglobin regulation may suggest new and better ways of attaining this goal.
-
inhibition of lsd1 by small molecule inhibitors stimulates Fetal Hemoglobin synthesis
Blood, 2019Co-Authors: Cuong Quang Le, Martin H. Steinberg, David H K Chui, Greggory Myers, Alawi Habara, Natee Jearawiriyapaisarn, George J Murphy, James Douglas EngelAbstract:TO THE EDITOR: Increased Fetal Hemoglobin (HbF) leads to diminished severity of sickle cell disease (SCD), as HbF disrupts deoxygenated sickle Hemoglobin polymerization.[1][1] Many efforts have been made to identify an effective way to increase HbF in adults that include using chemical inducers,[2
-
Fetal Hemoglobin in sickle cell anemia
Blood, 2011Co-Authors: Idowu Akinsheye, Abdulrahman Alsultan, Nadia Solovieff, Clinton T Baldwin, Paola Sebastiani, David H K Chui, Martin H. SteinbergAbstract:Fetal Hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle Hemoglobin polymer. Fetal Hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBB-like gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers.
-
Sickle Cell Anemia and Fetal Hemoglobin
The American Journal of the Medical Sciences, 1994Co-Authors: Martin H. SteinbergAbstract:ABSTRACT Fetal Hemoglobin, the predominant Hemoglobin of the fetus, is good for sickle cell anemia. This Hemoglobin inhibits the polymerization of sickle Hemoglobin. Clinical studies have shown that at any level of Fetal Hemoglobin, the more that is present, the better off is the patient. We are now able to increase Fetal Hemoglobin levels by pharmacologic means. We should know shortly if this is associated with clinical benefit.
Bernard G. Forget - One of the best experts on this subject based on the ideXlab platform.
-
molecular basis of hereditary persistence of Fetal Hemoglobin
Annals of the New York Academy of Sciences, 1998Co-Authors: Bernard G. ForgetAbstract:: Increased levels of Fetal Hemoglobin (HbF) can ameliorate the clinical course of inherited disorders of beta-globin gene expression, such as beta thalassemia and sickle cell anemia. In a group of disorders called hereditary persistence of Fetal Hemoglobin (HPFH), expression of the gamma-globin gene of HbF persists at high levels in adult erythroid cells. Molecular studies of the HPFH syndromes have identified several important regulatory elements for the normal pattern of gamma-globin gene expression. Deletion as well as nondeletion types of HPFH have been identified. The nondeletion types of HPFH are characterized by the presence of point mutations, in the promoter region of one or another gamma-globin gene, that are thought to alter interactions between various transcription factors and the promoter. The deletion types of HPFH are thought to deregulate the normal developmental pattern of gamma-globin gene expression due to the juxtaposition of normally distant cis-acting factors into the vicinity of the gamma genes. These findings have provided us with a more sophisticated understanding of the molecular basis for the persistent gamma-gene expression in these syndromes and point to certain strategies for potential future attempts at gene therapy for beta-globin gene disorders.
-
δβ Thalassemia and Hereditary Persistence of Fetal Hemoglobin
Hematology-oncology Clinics of North America, 1991Co-Authors: Jacques A. Bollekens, Bernard G. ForgetAbstract:δβ Thalassemia and hereditary persistence of Fetal Hemoglobin (HPFH) constitute a heterogeneous group of disorders characterized by absent or reduced synthesis of adult Hemoglobin (Hb A) and increased synthesis of Fetal Hemoglobin (Hb F). Coinheritance of these disorders with other β chain Hemoglobinopathies, such as β thalassemia and the sickle cell (βs) gene, can result in attenuation of the clinical severity of these Hemoglobinopathies owing to the increased Hb F levels. The molecular basis of these disorders is quite heterogeneous and consists of both deletion and nondeletion types of mutations. The characterization of these molecular defects has provided new insights on the structure and function of important regulatory elements that are involved in the normal control of expression of the β- and γ- globin genes and in Hemoglobin switching.
David H K Chui - One of the best experts on this subject based on the ideXlab platform.
-
inhibition of lsd1 by small molecule inhibitors stimulates Fetal Hemoglobin synthesis
Blood, 2019Co-Authors: Cuong Quang Le, Martin H. Steinberg, David H K Chui, Greggory Myers, Alawi Habara, Natee Jearawiriyapaisarn, George J Murphy, James Douglas EngelAbstract:TO THE EDITOR: Increased Fetal Hemoglobin (HbF) leads to diminished severity of sickle cell disease (SCD), as HbF disrupts deoxygenated sickle Hemoglobin polymerization.[1][1] Many efforts have been made to identify an effective way to increase HbF in adults that include using chemical inducers,[2
-
Fetal Hemoglobin in sickle cell anemia
Blood, 2011Co-Authors: Idowu Akinsheye, Abdulrahman Alsultan, Nadia Solovieff, Clinton T Baldwin, Paola Sebastiani, David H K Chui, Martin H. SteinbergAbstract:Fetal Hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle Hemoglobin polymer. Fetal Hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBB-like gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers.
Renzo Galanello - One of the best experts on this subject based on the ideXlab platform.
-
compound heterozygosity for klf1 mutations associated with remarkable increase of Fetal Hemoglobin and red cell protoporphyrin
Haematologica, 2011Co-Authors: Stefania Satta, Lucia Perseu, Isadora Asunis, Annalisa Cabriolu, L Maccioni, Franca Rosa Demartis, Laura Manunza, Renzo GalanelloAbstract:The persistence of high Fetal Hemoglobin level in adults may ameliorate the clinical phenotype of beta-thalassemia and sickle cell anemia. Several genetic variants responsible for hereditary persistence of Fetal Hemoglobin, linked and not linked to the beta globin gene cluster, have been identified in patients and in normal individuals. Monoallelic loss of KLF1, a gene with a key role in erythropoiesis, has been recently reported to be responsible for persistence of high levels of Fetal Hemoglobin. In a Sardinian family, high levels of HbF (22.1–30.9%) were present only in compound heterozygotes for the S270X nonsense and K332Q missense mutations, while the isolated S270X nonsense (haploinsufficiency) or K332Q missense mutation were associated with normal HbF levels (<1.5%). Functionally, the K332Q Klf1 mutation impairs binding to the BCl11A gene and activation of the γ- and β-globin promoters. Moreover, we report for the first time the association of KLF1 mutations with very high levels of zinc protoporphyrin.
A W Nienhuis - One of the best experts on this subject based on the ideXlab platform.
-
augmentation by erythropoietin of the Fetal Hemoglobin response to hydroxyurea in sickle cell disease
The New England Journal of Medicine, 1993Co-Authors: Griffin P Rodgers, George J. Dover, Nobuhiro Uyesaka, Constance Tom Noguchi, Alan N Schechter, A W NienhuisAbstract:Background Hydroxyurea increases the production of Fetal Hemoglobin in patients with sickle cell anemia, inhibiting the polymerization of Hemoglobin S and potentially improving vaso-occlusive manifestations and hemolysis. Recombinant erythropoietin increases the number of reticulocytes containing Fetal Hemoglobin in laboratory animals and in humans. We studied whether hydroxyurea and erythropoietin might have a potentiating effect on the production of Fetal Hemoglobin in patients with sickle cell disease. Methods We treated four patients who were receiving hydroxyurea for sickle cell disease (three who were homozygous for sickle cell anemia and one with sickle β0-thalassemia) with escalating doses of intravenous erythropoietin for seven weeks, along with oral iron sulfate. Doses of hydroxyurea on four consecutive days were alternated with doses of erythropoietin on three consecutive days. Results There was a 28 percent increase in the number of reticulocytes containing Fetal Hemoglobin and a 48 percent in...