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Globin Gene (globin + gene)

Distribution by Scientific Domains

Medical Sciences	77%
Life Sciences	22%

Terms modified by Globin Gene

globin gene expression

Selected Abstracts

Co-inheritance of Hb Hershey [,70(E14) Ala,Gly] and Hb La Pommeraie [,133(H11)Val,Met] in a Sicilian subject

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2010
Antonino Giambona
Abstract Objectives:,This report represents the first observation in Sicily of two rare , -globin gene variants, Hb Hershey [,70(E14) Ala,Gly] and Hb La Pommeraie [,133(H11)Val,Met], found in a 35-year-old male patient from Messina, in the north-east of Sicily during population screening for hemoglobinopathies. Methods: The occurrence of the Hb variants was assessed by cation exchange chromatography while complete blood counts were obtained using automatic cell counters. Red cell lysates were analyzed by electrophoresis at alkaline and acid pH. Stability of hemoglobin was checked by the isopropanol precipitation test and by the heat tests while inclusion bodies and reticulocyte count were determined by incubation of blood samples with brilliant cresyl blue. Molecular analysis was performed by DNA sequencing of ,- and , -globin genes. Results: We observed an abnormally high performance liquid chromatography elution with a slight reduction in mean corpuscular volume and mean corpuscular haemoglobin parameters and mutations at codon 70 GCC,GGC (Hb Hershey) and at codon 133 GTG,ATG (Hb La Pommeraie) in , -globin gene. Conclusion: Family analysis of three generations demonstrated the presence of these two mutations in trans. So it was possible to describe the phenotypes of these variants in a heterozygous state and in double heterozygous state. [source]

Production of ,-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous ,039 thalassemia patients,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2009
Francesca Salvatori
In several types of thalassemia (including ,039-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying ,-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the ,039-thalassemia globin gene under control of the ,-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of ,-globin by K562 cell clones expressing the ,039-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from ,039-thalassemia patients were demonstrated to be able to produce ,-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of ,0 -thalassemia caused by stop codon mutations. Am. J. Hematol., 2009. © 2009 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]

Severe ,0 thalassemia/hemoglobin E disease caused by de novo 22-base pair duplication in the paternal allele of , globin gene

AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2007
Ponlapat Rojnuckarin
Abstract , Thalassemia is a major public health concern in Southeast Asia. A prevention program has been implemented in Thailand comprising mass carrier screening and genetic testing. In this study, a Thai girl with severe , thalassemia/hemoglobin (Hb) E disease was born from the mother with Hb E trait and the genotypically normal father. DNA sequencing revealed novel 22-bp tandem duplication in the paternal allele of , globin gene, producing a severely truncated product. A short recurring nucleotide at the insertion site suggested a predisposition to this mutation. Therefore, spontaneous , globin mutations occasionally occur in normal population. Its clinical significance is noteworthy in countries with high prevalence of , thalassemia. Am. J. Hematol 2007. © 2006 Wiley-Liss, Inc. [source]

Hb Florida: A novel elongated C-terminal ,-globin variant causing dominant ,-thalassemia phenotype

AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2006
B.I. Weinstein
Abstract We report here a new frameshift mutation in exon 3 of the ,-globin gene, a single nucleotide deletion (-C) in between codons 140/141 (GCC/CTG,GCC/TG), found in an 8-year-old Argentinean girl with clinical picture of thalassemia intermedia. It leads to a ,-chain that is elongated to 156 amino acids [(141)Trp-Pro-Thr-Ser-Ile-Thr-Lys-Leu-Ala-Phe-Leu-Leu-Ser-Asn-Phe-(156)Tyr-COOH]. The resulting hemoglobin, which we named Hb Florida, was not detected in peripheral blood; however, erythroid hyperplasia and dyserythropoiesis with large inclusion bodies on methyl violet staining were observed in bone marrow, suggesting that this is a hyperunstable variant producing a dominant ,-thalassemia phenotype, since the other ,-allele was completely normal. Am. J. Hematol. 81:358,360, 2006. © 2006 Wiley-Liss, Inc. [source]

Molecular characterization of sickle cell anemia in the Northern Brazilian state of Pará

AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2010
Greice De Lemos Cardoso
To assess ,+-thalassemia deletion alleles, ,-thalassemia mutations and haplotypes linked to the HBB*S cluster in a sample of 130 unrelated sickle cell anemia (SCA) patients (55% female) from Belém, Pará State, for their possible effects on the patients' survival. -,3.7, -,42, -,20.5, and ,MED ,+-thalassemia deletion alleles were investigated using multiplex gap-PCR method. Characterization of ,-thalassemia mutations was made by direct genomic sequencing of the ,-globin gene amplified through polymerase chain reaction (PCR). Haplotypes were determined by analysis of six polymorphic restriction sites [(1) XmnI-5,,G, (2) HindIII-,G, (3) HindIII-,A, (4) HincII-,,, (5) HincII-3,,,, and (6) HinfI-5,,] followed by restriction digestion and agarose gel electrophoresis. Twenty-one patients (16%) presented -,3.7 thalassemia. Sixteen of those (76%) were heterozygous (-,3.7/,,) and 5 (24%) were homozygous (-,3.7/-,3.7). -,4.2, -,20.5 and ,MED deletions were not found. Nine cases of sickle cell-, thalassemia were found and four different ,-thal mutations were identified: ,+ ,88 (C>T), 3.8%; ,+ codon 24 (T > A), 1.5%; ,+ IVSI-110 (G > A), 0.7% and , (IVSI-1 (G > A), 0.7%. No differences according to age were observed in -,3.7 deletion, ,-thalassemia and HHB*S haplotypes distribution. Our results suggest that although ,- and ,-thalassemia and ,S haplotypes may have modulating effect on clinical expression and hematological parameters of SCA, these genetic variables probably have little influence on the subjects' survival. Am. J. Hum. Biol. 22:573,577, 2010. © 2010 Wiley-Liss, Inc. [source]

Cell-free fetal DNA (SRY locus) concentration in maternal plasma is directly correlated to the time elapsed from the onset of preeclampsia to the collection of blood

PRENATAL DIAGNOSIS, Issue 4 2004
Antonio Farina MD
Abstract Objective To determine (1) if fetal DNA (fDNA) in the maternal circulation in women affected by preeclampsia correlates with the time elapsed from the onset of symptoms to the time of blood collection, and (2) if the inclusion of this variable improves the discrimination between affected and unaffected patients by using fDNA distributions. Methods Plasma were collected from 34 women at 33.7 ± 3.9 weeks' gestation, affected by preeclampsia, and bearing a single male fetus. fDNA was extracted from 1.5-mL plasma samples, and the SRY and ,-globin gene were analyzed by real-time quantitative PCR. MoMs (multiple of the control median) were calculated by using a log equation of 102 normal cases. Log MoMs were then plotted against the time elapsed from onset of symptoms to blood collection (expressed in days) by means of a log-linear regression. Adjusted MoMs were then calculated. ROC curves were used to test the discrimination obtained by using adjusted MoMs. Results The median MoMs of controls and preeclamptic patients were 1.00 ± 1.53 and 2.62 ± 2.70 respectively. By plotting log MoM fDNA against the time elapsed from onset of symptoms to blood collection, we found a significant positive correlation, (p -value < 0.001, R2 = 0.55, F = 38.97, from 1 to 50 days). The adjusted median fDNA MoM was 2.66 ± 2.50. Areas under the curves, as estimated by ROC curves, were 76.7 for unadjusted and 85.5 for adjusted MoMs respectively (p -value = 0.02). Conclusions The effect of a further covariate showed that (1) fDNA passage from trophoblasts to maternal circulation for unit of time is proportional to the duration of the damage and that (2) increased discrimination can be obtained in comparison to normal subjects. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Increased cell-free DNA concentrations in patients with obstructive sleep apnea

PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 6 2008
Chol Shin md
Aim:, Blood concentrations of cell-free DNA, which is considered to be released during apoptosis, are elevated under some pathological conditions such as cardiovascular disease and cancer. The association between obstructive sleep apnea (OSA) and cell-free DNA concentrations has not been reported so far. The purpose of the present study was to examine the association between OSA and plasma DNA concentrations. Methods:, A case,control study was conducted using a total of 164 men aged 39,67 years, who were free of coronary heart disease and cancer. Laboratory-based overnight polysomnography was performed for all participants. Results:, On the basis of polysomnography, patients with an apnea,hypopnea index (AHI) = 5,30 events/h were defined as having mild,moderate OSA (n = 33) and those with >30 events/h were defined as having severe OSA (n = 49). All 82 controls had AHI < 5 events/h. Plasma DNA concentrations from all participants were analyzed for the ,-globin gene using fluorescence-based real-time polymerase chain reaction. Patients with severe OSA had significantly higher plasma DNA concentrations than persons with mild,moderate OSA and those without OSA (P < 0.05). AHI was significantly associated with body mass index (P < 0.001), hypertension (P < 0.001), and plasma DNA concentration (P < 0.05). Conclusion:, After taking into account hypertension and other potential risk factors, persons with high plasma DNA concentrations (>8 µg/L) had approximately fourfold higher odds of OSA than those with low DNA levels. Further data are warranted to confirm the association for men and to evaluate the association for women. [source]

research paper: Role of the cold shock domain protein A in the transcriptional regulation of HBG expression

BRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2010
Raffaella Petruzzelli
Summary Impaired switching from fetal haemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal haemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate ,-thalassaemia and sickle cell anaemia. Fetal haemoglobin levels are regulated by complex mechanisms involving factors linked or not to the ,-globin gene (HBB) locus. To search for factors putatively involved in the expression of the ,-globin genes (HBG1, HBG2), we examined the reticulocyte transcriptome of three siblings who had different HbF levels and different degrees of ,-thalassaemia severity although they had the same ,BA - and ,,B cluster genotypes. By mRNA differential display we isolated the cDNA coding for the cold shock domain protein A (CSDA), also known as dbpA, previously reported to interact in vitro with the HBG2 promoter. Expression studies performed in K562 and in primary erythroid cells showed an inverse relationship between HBG and CSDA expression levels. Functional studies performed by Chromatin Immunoprecipitation and reporter gene assays in K562 cells demonstrated that CSDA is able to bind the HBG2 promoter and suppress its expression. Therefore, our study demonstrated that CSDA is a trans-acting repressor factor of HBG expression and modulates the HPFH phenotype. [source]

Human ,2-globin nonsense-mediated mRNA decay induced by a novel , -thalassaemia frameshift mutation at codon 22

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006
Francisco J. C. Pereira
Summary We describe a novel , -thalassaemia determinant in a 3-year-old girl presenting a mild microcytic and hypochromic anaemia, and normal haemoglobin A2 level. Molecular studies revealed heterozygosity for a novel microdeletion (,C) at codon 22 of the ,2 -globin gene. As the frameshift mutation generates a premature translation termination codon at position 48/49, we investigated the effect of the nonsense codon on the ,2 -globin gene expression. Although it does not affect RNA splicing, the premature nonsense codon induces accelerated mRNA degradation. To our knowledge, this is the first time the nonsense-mediated mRNA decay has been reported to occur in human , -globin mRNA. [source]

,-Thalassaemia intermedia in a Turkish girl: homozygosity for G,A substitution at +22 relative to the ,-globin cap site

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2001
R. Öner
We provide the first description of a homozygote patient for the G,A substitution in the 5, UTR of the ,-globin gene. The proband was a 17-year-old girl with ,-thalassaemia intermedia who had never received a blood transfusion. The physical examination revealed a well-developed women with no facial or bony abnormalities. There was mild paleness and mild splenomegaly which was 2 cm below the costal margin. The haemoglobin (Hb) was 7·6 g/dl, Hb A2 5·4% and Hb F 14·6% of the total Hb. The Hb A2 of both parents was 3·5%. The Hb F level in the mother and father were 0·9, 1·2% and the mean cell volume (MCV) value was 70 and 72 fl respectively. DNA analysis of the ,-gene region of the propositus revealed homozygosity for a G,A substitution at nucleotide +22 relative to the ,-gene cap site, within a functional downstream region that was referred to as the DCE (downstream core element). In addition to the data obtained previously from in vitro transcription assays, clinical findings and in vivo expression studies gave some valuable clues about the effect of +22 G,A mutation on the expression of ,-gene. Phenotypic expression of this homozygous patient is highly suggestive that G,A substitution at nt +22 confers a relatively mild (silent) ,+ -thalassaemia phenotype. [source]

A novel AATAAA,CATAAA mutation at the polyadenylation site of the ,-globin gene

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2001
S. K. Ma
First page of article [source]

Co-inheritance of Hb Hershey [,70(E14) Ala,Gly] and Hb La Pommeraie [,133(H11)Val,Met] in a Sicilian subject

Distribution and frequency of , -thalassemia mutations in northwestern and central Greece

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2003
I. Georgiou
Abstract: Objectives : , -Thalassemia is a common autosomal recessive disorder resulting from over 200 different mutations of the , -globin genes. The spectrum of , -thalassemia mutations in Greece has been previously described in the population of the capital city of Athens, or in , -thalassemia patients having transfusion therapy. The aim of the present study was to identify the distribution of the most common , -thalassemia mutations in the population of northwestern and central Greece. Methods : The data for this study were derived from a total of 1130 unrelated subjects including 46 , -thalassemia major, three , -thalassemia intermedia and 1081 carriers identified in our antenatal screening program. , -Thalassemia mutations were identified by ARMS, DGGE and Reverse Dot Blot. Results : The most common mutation, IVS-I-110, is followed, in order of frequency, by the mutations Cd-39, IVS-I-1, IVS-II-1, Cd-6, IVS-I-6, IVS-I-5, IVS-II-745, Cd-5 and 44 bp del. IVS-I-110 and Cd-39 frequencies are similar with those found in other Balkan countries. Significant differences in regional distribution were observed. The results showed a clear drift of the distribution of the most frequent IVS-I-110 mutation in the south,north (29.4, 40.0, 44.6 and 61.7%) and the east,west axis (31.8 and 44.6%). Conclusions : Population screening and prenatal diagnosis are significantly facilitated by these data. Furthermore, the detailed distribution tables of , -thalassemia mutations are essential for counseling and extraction of genetic diversity estimates for population genetic studies in other inherited disorders. [source]

THE EVOLUTION OF THE VERTEBRATE ,-GLOBIN GENE PROMOTER

EVOLUTION, Issue 2 2002
Nadia A. Chuzhanova
Abstract Complexity analysis is capable of highlighting those gross evolutionary changes in gene promoter regions (loosely termed "promoter shuffling") that are undetectable by conventional DNA sequence alignment. Complexity analysis was therefore used here to identify the modular components (blocks) of the orthologous ,-globin gene promoter sequences of 22 vertebrate species, from zebrafish to humans. Considerable variation between the ,-globin gene promoters was apparent in terms of block presence/absence, copy number, and relative location. Some sequence blocks appear to be ubiquitous, whereas others are restricted to a specific taxon. Block similarities were also evident between the promoters of the paralogous human ,-like globin genes. It may be inferred that a wide variety of different mutational mechanisms have operated upon the ,-globin gene promoter over evolutionary time. Because these include gross changes such as deletion, duplication, amplification, elongation, contraction, and fusion, as well as the steady accumulation of single base-pair substitutions, it is clear that some redefinition of the term "promoter shuffling" is required. This notwithstanding, and as previously described for the vertebrate growth hormone gene promoter, the modular structure of the ,-globin promoter region and those of its paralogous counterparts have continually been rearranged into new combinations through the alteration, or shuffling, of preexisting blocks. Some of these changes may have had no influence on promoter function, but others could have altered either the level of gene expression or the responsiveness of the promoter to external stimuli. The comparative study of vertebrate ,-globin gene promoter regions described here confirms the generality of the phenomenon of sequence block shuffling and thus supports the view that it could have played an important role in the evolution of differential gene expression. [source]

Molecular diagnosis of inherited disorders: lessons from hemoglobinopathies,

HUMAN MUTATION, Issue 5 2005
George P. Patrinos
Abstract Hemoglobinopathies constitute a major health problem worldwide, with a high carrier frequency, particularly in certain regions where malaria has been endemic. These disorders are characterized by a vast clinical and hematological phenotypic heterogeneity. Over 1,200 different genetic alterations that affect the DNA sequence of the human ,-like (HBZ, HBA2, HBA1, and HBQ1) and ,-like (HBE1, HBG2, HBG1, HBD, and HBB) globin genes are mainly responsible for the observed clinical heterogeneity. These mutations, together with detailed information about the resulting phenotype, are documented in the globin locus-specific HbVar database. Family studies and comprehensive hematological analyses provide useful insights for accurately diagnosing thalassemia at the DNA level. For this purpose, numerous techniques can provide accurate, rapid, and cost-effective identification of the underlying genetic defect in affected individuals. The aim of this article is to review the diverse methodological and technical platforms available for the molecular diagnosis of inherited disorders, using thalassemia and hemoglobinopathies as a model. This article also attempts to shed light on issues closely related to thalassemia diagnostics, such as prenatal and preimplantation genetic diagnoses and genetic counseling, for better-quality disease management. Hum Mutat 26(5), 399,412, 2005. © 2005 Wiley-Liss, Inc. [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]

Haemoglobin H disease due to (,,,SEA) ,-globin gene deletion and ,2-codon 30 (,GAG) mutation: a family study

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2001
S.K. Ma
A Chinese family in which two siblings suffer from haemogloblin (Hb) H disease due to (,,,SEA) ,-globin gene deletion and ,2-codon 30 (,GAG) mutation is described. Both siblings are transfusion-independent and have survived to adulthood. In contrast to previous report of hydrops fetalis associated with ,-,-thal-1 and ,2-codon 30 (,GAG) mutation, the ,-globin genes are intact in the two siblings, which most probably alleviates the ,-chain excess and protects the fetus from severe anaemia. Correlation of genotype with phenotype in Hb H disease is important for genetic counselling, especially in the antenatal setting. [source]

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]

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

Embryonic and fetal globins are expressed in adult erythroid progenitor cells and in erythroid cell cultures

PRENATAL DIAGNOSIS, Issue 7 2001
Elizabeth T. Lau
Abstract The understanding of human hemoglobin ontogeny during development is of biological and clinical importance. Molecular and immunocytological techniques were used to study the expression of embryonic zeta (,), epsilon (,), and fetal gamma (,) globin genes in newborn cord blood, peripheral blood from men, pregnant and non-pregnant women, and in vitro mononuclear cell cultures. We have shown that embryonic and fetal globin mRNA and peptides are expressed in cultured erythroid cells and in circulating blood cells from newborns, adult non-pregnant women and from men. The findings suggest that during erythroid cell differentiation in newborns and adults, there is a transient recapitulation of sequential globin chain expression as found during embryonic and fetal development. Furthermore, these findings underscore the need for caution in using embryonic and fetal globin chains as markers to identify erythroid cells of fetal origin in maternal circulation for prenatal diagnosis. Copyright © 2001 John Wiley & Sons, Ltd. [source]

research paper: Role of the cold shock domain protein A in the transcriptional regulation of HBG expression

Chronic and severe haemolytic anaemia caused by co-inheritance of , -thalassaemia and triplicated , -globin genes

BRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2007
Chen Wang
No abstract is available for this article. [source]

Leukemia-related transcription factor TEL/ETV6 expands erythroid precursors and stimulates hemoglobin synthesis

CANCER SCIENCE, Issue 4 2009
Minenori Eguchi-Ishimae
TEL/ETV6 located at chromosome 12p13 encodes a member of the E26 transformation-specific family of transcription factors. TEL is known to be rearranged in a variety of leukemias and solid tumors resulting in the formation of oncogenic chimeric protein. Tel is essential for maintaining hematopoietic stem cells in the bone marrow. To understand the role of TEL in erythropoiesis, we generated transgenic mice expressing human TEL under the control of Gata1 promoter that is activated during the course of the erythroid-lineage differentiation (GATA1-TEL transgenic mice). Although GATA1-TEL transgenic mice appeared healthy up to 18 months of age, the level of hemoglobin was higher in transgenic mice compared to non-transgenic littermates. In addition, CD71+/TER119+ and c-kit+/CD41+ populations proliferated with a higher frequency in transgenic mice when bone marrow cells were cultured in the presence of erythropoietin and thrombopoietin, respectively. In transgenic mice, enhanced expression of Alas-e and ,-major globin genes was observed in erythroid-committed cells. When embryonic stem cells expressing human TEL under the same Gata1 promoter were differentiated into hematopoietic cells, immature erythroid precursor increased better compared to controls as judged from the numbers of burst-forming unit of erythrocytes. Our findings suggest some roles of TEL in expanding erythroid precursors and accumulating hemoglobin. (Cancer Sci 2009; 100: 689,697) [source]