Ignite Creation Date:
2024-06-16 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06440603
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-04
First Post:
2024-05-19
Brief Title:
EKLF Gene Expression in β-thalassemia
Sponsor:
Rofaida Hassan Ahmed
Organization:
Assiut University
Study Overview
Official Title:
Erythroid Krüppel Like Factor EKLF Gene Expression in β-thalassemia Patients
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
1 Studying the effect of expression pattern of EKLF gene in β-thalassemic patients
2 Detecting the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients
2 Detecting the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients
Detailed Description:
β-thalassemia is a common inherited disorder caused by absent or reduced synthesis of the hemoglobin subunit beta beta globin chain it has 3 clinical types minor which is a carrier state intermedia and major which are differentiated by blood transfusion dependency and lab findings
In β-thalassemia insufficient production of the β-globin molecule results in an excess of free α-globin chains that can precipitate within erythroid precursors impairing their maturation and leads to death of these precursors and ineffective production of erythroid cells As a result a significant anaemia occurs and the consequent expansion of erythroid precursors can lead to secondary problems in bones and other organs
These mutations are primarily point mutations that affect transcriptional control translation and splicing of the beta haemoglobin gene and gene expression
The frequency of beta-thalassemia mutations varies by regions of the world with the highest prevalence in the Mediterranean the Middle East and Southeast and Central Asia Approximately 68000 children are born with beta-thalassemia Its prevalence is 80-90 million carriers around 15 of the global population
Erythroid Krüppel-like factor EKLF or KLF1 is a transcriptional regulator that plays a major role in lineage-restricted control of gene expression KLF1 expression and activity are tightly controlled in a temporal and differentiation stage-specific manner The mechanisms by which KLF1 is regulated encompass a range of biological processes including control of KLF1 RNA transcription protein stability localization and posttranslational modifications Intact KLF1 regulation is essential to correctly regulate erythroid function by gene transcription and to maintain hematopoietic lineage homeostasis by ensuring a proper balance of erythroidmegakaryocytic differentiation In turn KLF1 regulates erythroid biology by a wide variety of mechanisms including gene activation and repression by regulation of chromatin configuration transcriptional initiation and elongation and localization of gene loci to transcription factories in the nucleus
Previous studies have shown that EKLF plays a critical role in regulating the developmental switch between fetal and adult haemoglobin expression both by direct activation of β-globin and indirect repression of γ-globin gene expression in adult erythroid progenitors via regulation of Bcl11a and ZBTB7a and PUM1
PUM1 is a direct posttranscriptional regulator of β-globin switching whose expression is regulated by the erythroid master transcription factor erythroid Krüppel-like factor EKLFKLF1 peaks during erythroid differentiation binds γ-globin messenger RNA mRNA and reduces γ-globin HBG1 mRNA stability and translational efficiency which culminates in reduced γ-globin protein levels
So EKLF is too important in erythropoiesis and Hb switching that there are clinical trials nowadays depending on the molecules that targeted by EKLF egBcl11a ZBTB7a and PUM1 and their role in Hb switching in treatment of thalassemia and other haemolytic anaemias as sickle cell anaemia
In β-thalassemia insufficient production of the β-globin molecule results in an excess of free α-globin chains that can precipitate within erythroid precursors impairing their maturation and leads to death of these precursors and ineffective production of erythroid cells As a result a significant anaemia occurs and the consequent expansion of erythroid precursors can lead to secondary problems in bones and other organs
These mutations are primarily point mutations that affect transcriptional control translation and splicing of the beta haemoglobin gene and gene expression
The frequency of beta-thalassemia mutations varies by regions of the world with the highest prevalence in the Mediterranean the Middle East and Southeast and Central Asia Approximately 68000 children are born with beta-thalassemia Its prevalence is 80-90 million carriers around 15 of the global population
Erythroid Krüppel-like factor EKLF or KLF1 is a transcriptional regulator that plays a major role in lineage-restricted control of gene expression KLF1 expression and activity are tightly controlled in a temporal and differentiation stage-specific manner The mechanisms by which KLF1 is regulated encompass a range of biological processes including control of KLF1 RNA transcription protein stability localization and posttranslational modifications Intact KLF1 regulation is essential to correctly regulate erythroid function by gene transcription and to maintain hematopoietic lineage homeostasis by ensuring a proper balance of erythroidmegakaryocytic differentiation In turn KLF1 regulates erythroid biology by a wide variety of mechanisms including gene activation and repression by regulation of chromatin configuration transcriptional initiation and elongation and localization of gene loci to transcription factories in the nucleus
Previous studies have shown that EKLF plays a critical role in regulating the developmental switch between fetal and adult haemoglobin expression both by direct activation of β-globin and indirect repression of γ-globin gene expression in adult erythroid progenitors via regulation of Bcl11a and ZBTB7a and PUM1
PUM1 is a direct posttranscriptional regulator of β-globin switching whose expression is regulated by the erythroid master transcription factor erythroid Krüppel-like factor EKLFKLF1 peaks during erythroid differentiation binds γ-globin messenger RNA mRNA and reduces γ-globin HBG1 mRNA stability and translational efficiency which culminates in reduced γ-globin protein levels
So EKLF is too important in erythropoiesis and Hb switching that there are clinical trials nowadays depending on the molecules that targeted by EKLF egBcl11a ZBTB7a and PUM1 and their role in Hb switching in treatment of thalassemia and other haemolytic anaemias as sickle cell anaemia
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None