EKLF Gene Expression in β-thalassemia

May 31, 2024 updated by: Rofaida Hassan Ahmed

Erythroid Krüppel Like Factor (EKLF) Gene Expression in β-thalassemia Patients

  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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 1.5% 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 erythroid/megakaryocytic 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 (EKLF/KLF1), 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 (eg:Bcl11a, ZBTB7a and PUM1) and their role in Hb switching in treatment of thalassemia and other haemolytic anaemias as sickle cell anaemia.

Study Type

Observational

Enrollment (Estimated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Patients > 5 years diagnosed with β-thalassemia including both thalassemia major and intermedia

Description

Inclusion Criteria:

  • patients with β-thalassemia (major and intermedia).
  • patients are of both sexes (male or female) at any age

Exclusion Criteria:

  • patients with any other types of hemolytic anaemia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group I
Age and sex matched healthy Control
Diagnostic test: PCR

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for detection of EKLF:

  • The method of total RNA extraction: TRIZOL and TRIZOL LS.
  • The purity and concentration of the RNA will be measured using Nano Drop 2000 instument.
  • cDNA will be done with primers using thr Goscript Reverse Transcription System
Group 2
50 patients with β-thalassemia major
Diagnostic test: PCR

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for detection of EKLF:

  • The method of total RNA extraction: TRIZOL and TRIZOL LS.
  • The purity and concentration of the RNA will be measured using Nano Drop 2000 instument.
  • cDNA will be done with primers using thr Goscript Reverse Transcription System
Group 3
50 patients with β-thalassemia intermedia
Diagnostic test: PCR

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for detection of EKLF:

  • The method of total RNA extraction: TRIZOL and TRIZOL LS.
  • The purity and concentration of the RNA will be measured using Nano Drop 2000 instument.
  • cDNA will be done with primers using thr Goscript Reverse Transcription System

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
study the expression pattern of EKLF gene in β-thalassemic patients, work by measuring mRNA levels
Time Frame: Baseline
study the expression pattern of EKLF gene by Real-time polymerase chain reaction (RT-qPCR) in β-thalassemic patients
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
study the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients.
Time Frame: Baseline
study the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rofaida Hassan Ahmed

Investigators

  • Study Director: Eman Naser Eldin, Assiut University
  • Study Director: Sherif Helmy, Assiut University
  • Study Director: Reem Elagoz, Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2024

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

May 19, 2024

First Submitted That Met QC Criteria

May 31, 2024

First Posted (Estimated)

June 4, 2024

Study Record Updates

Last Update Posted (Estimated)

June 4, 2024

Last Update Submitted That Met QC Criteria

May 31, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • β-thalassemia

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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