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Fetal Hemoglobin (fetal + hemoglobin)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Disorders of the synthesis of human fetal hemoglobin

IUBMB LIFE, Issue 2 2008
Laura Manca
Abstract Fetal hemoglobin (HbF), the predominant hemoglobin in the fetus, is a mixture of two molecular species (,2G,2 and ,2A,2) that differ only at position 136 reflecting the products of two nonallelic ,-globin genes. At the time of birth, HbF accounts for ,70% of the total Hb. The G,:A, globin ratio in the HbF of normal newborn is 70:30 whereas in the trace amounts of HbF that is found in the adult it reverses to 40:60 because of a ,- to ,-globin gene switch. Alterations of these ratios are indicative of a molecular defect at the level of the HbF synthesis. Qualitative hemoglobinopathies due to G, and A, chain structural variants, and quantitative hemoglobinopathies affecting the synthesis of HbF such as ,-thalassemias, duplications, triplications, and even sextuplications of the ,-globin genes, which may be detected in newborn blood lysates, have been described. Moreover, several pathological and nonpathological conditions affecting the ,-globin gene cluster, such as ,-thalassemia, sickle cell disease, ,,-thalassemia, and hereditary persistence of HbF syndromes, are characterized by the continued synthesis of ,-globin chains in the adult life. Studies of these natural mutants associated with increased synthesis of HbF in adult life have provided considerable insight into the understanding of the control of globin gene expression and Hb switching. © 2008 IUBMB IUBMB Life, 60(2): 94,111, 2008 [source]

Delayed decline of , -globin expression in infant age associated with the presence of G,,158 (C,T) polymorphism

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2008
M. GROSSO
Summary Persistent production of fetal hemoglobin (HbF) in adult has ameliorative effects on hemoglobinopathies and great efforts are currently made to achieve an exhaustive understanding of the molecular mechanisms of the switching in globin gene expression. One of the factors reported to be associated with the expression of fetal globin genes is the Xmn I G,,158 polymorphism, although it is still unclear if it is involved in this mechanism either by itself or in strong linkage disequilibrium with other loci. Here, we report a novel effect of the Xmn I G,,158 site that was found associated with a significant delayed decline of HbF production in infant age. The prolonged decay trend was enhanced when the G,,158 C,T substitution was co-inherited with a , -thalassemic trait. Our observations reinforce the hypothesis that this region plays an important role in the expression of the , -globin genes and give new insights on the intriguing and still poorly understood mechanisms of globin gene expression switching. [source]

Disorders of the synthesis of human fetal hemoglobin

Phase I study of decitabine with doxorubicin and cyclophosphamide in children with neuroblastoma and other solid tumors: A children's oncology group study,,

PEDIATRIC BLOOD & CANCER, Issue 4 2010
MRCP, Rani E. George MD
Abstract Background Demethylating agents may alter the expression of genes involved in chemotherapy resistance. We conducted a phase I trial to determine the toxicity and molecular effects of the demethylating agent, decitabine, followed by doxorubicin and cyclophosphamide in children with refractory solid tumors. Procedure Stratum A included children with any solid tumor; Stratum B included neuroblastoma patients only. Patients received a 1-hr decitabine infusion for 7 days, followed by doxorubicin (45,mg/m2) and cyclophosphamide (1,g/m2) on day 7. Pharmacokinetic studies were performed after the first dose of decitabine. Biological studies included methylation and gene expression analyses of caspase-8, MAGE-1 and fetal hemoglobin (HbF), and expression profiling of pre- and post-treatment peripheral blood and bone marrow cells. Results The maximum-tolerated dose of decitabine was 5,mg/m2/day for 7 days. Dose-limiting toxicities at 10,mg/m2/day were neutropenia and thrombocytopenia. Decitabine exhibited rapid clearance from plasma. Three of 9 patients in Stratum A and 4/12 patients in Stratum B had stable disease for ,4 months. Sustained MAGE-1 demethylation and increased HbF expression were observed in the majority of patients post-treatment (12/20 and 14/16, respectively). Caspase-8 promoter demethylation and gene expression were seen in 2/7 bone marrow samples. Differentially expressed genes were identified by microarray analysis. Conclusion Low-dose decitabine when combined with doxorubicin/cyclophosphamide has tolerable toxicity in children. However, doses of decitabine capable of producing clinically relevant biologic effects were not well tolerated with this combination. Alternative strategies of combining demethylating agents with non-cytotoxic, biologically targeted agents such as histone deactelyase inhibitors should be explored. Pediatr Blood Cancer. 2010;55:629,638. © 2010 Wiley-Liss, Inc. [source]

Hemoglobin Kenya composed of ,- and (A,,)-fusion-globin chains, associated with hereditary persistence of fetal hemoglobin

AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2009
Ibifiri Wilcox
Hb Kenya is made up of two normal ,-globin chains and two A,,-fusion globin chains. The latter are the product of an A,,-hybrid globin gene formed as a result of misalignment during meiosis and nonhomologous crossing over. It is associated with a deletion of 22.7 kb including the ,-globin gene, between the A,- and ,-globin genes. Hb Kenya is found in Kenyans and Ugandans. Heterozygotes have moderately increased Hb F, and this mutation has been known as an (A,,)+ hereditary persistence of fetal hemoglobin (HPFH). Compound heterozygotes for Hb Kenya/Hb S are thought to be asymptomatic, but reports of long term follow-up of these patients are lacking. The correct identification of Hb Kenya is sometimes problematic. In cation exchange high performance liquid chromatography, Hb Kenya elutes in similar position as Hb A2, Hb Lepore, Hb E, and several other variant hemoglobins. Definitive diagnosis that is necessary for proper patient management is best done by DNA-based gap-PCR tests. Am. J. Hematol, 2009. © 2008 Wiley-Liss, Inc. [source]

Compound heterozygosity of non-deletional hereditary persistence of fetal hemoglobin and ,,-thalassemia,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2008
Angelos Kalamaras
No abstract is available for this article. [source]

Induction of fetal hemoglobin synthesis by valproate: Modulation of MAPkinase pathways

AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2002
O. Witt
Abstract Valproate has been found to stimulate fetal hemoglobin (HbF) synthesis in patients with sickle cell disease. In accordance with these clinical observations, we found a moderate induction of HbF synthesis in K562 erythroid cells in vitro. Investigation of the role of the mitogen-activated protein kinase (MAPK) pathways by Western blot analysis and use of specific kinase inhibitors suggests that inhibition of ERK pathway and activation of the p38 pathway may contribute to the HbF-inducing activity of valproate. Am. J. Hematol. 71:45,46, 2002. © 2002 Wiley-Liss, Inc. [source]