Ignite Creation Date:
2024-05-06 @ 2:06 PM
Last Modification Date:
2024-10-26 @ 1:25 PM
Study NCT ID:
NCT04215822
Status:
UNKNOWN
Last Update Posted:
2020-01-03
First Post:
2019-12-30
Brief Title:
PHF19 Gene Expression and EZH2 Gene Deletion in Acute Myeloid Leukemia
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
PHF19 Gene Expression and EZH2 Gene Deletion as Potential Biomarkers of Acute Myeloid Leukemia
Status:
UNKNOWN
Status Verified Date:
2019-12
Last Known Status:
NOT_YET_RECRUITING
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:
The study aims to detect pattern of expression of PHF19 gene and EZH2 gene deletion in acute myeloid leukemia patients and detect their prognostic role on patients outcome
Detailed Description:
Acute Myeloid Leukemia AML is a heterogeneous clonal disorder characterized by immature myeloid cell proliferation and bone marrow failure Diagnosis of AML is based on morphological diagnosis with proliferation of blast cells 20 of bone marrow cells flow cytometric analysis and cytogenetic abnormalities
The etiological agent and pathogenesis of AML are not entirely clear only few AML cases can be accurately classified through traditional cellular morphological classification Thus it is very difficult to judge the disease condition and predict prognosis Improper expression of specific genes is a common finding in AML and may induce clinically relevant biological subsets Cytogenetic abnormalities and molecular alterations provide the most powerful prognostic information in AML Consequently identification of novel biomarkers which could predict outcome or guide treatment choice will make more contribution to the clinical management of AML
Gene repression is the deactivation of an active gene that causes shut down of transcription and it represents a powerful tool in controlling gene expression in order to prevent the metabolic dysregulation during the development or the differentiation program Polycomb repressive complex 2 PRC2 is the sole enzymatic complex capable of establishing gene-repression through high-degree methylation of histone H3 at lysine 27 H3K27 therefore it plays critical roles in regulation of normal hematopoiesis Enhancer of Zeste Homolog 2 EZH2 gene is the catalytic subunit of PRC2 located on chromosome 7q361 EZH2 gene encode EZH2 methyltransferase which mediates transcriptional inactivation through trimethylation of lysine 27 of histone H3 H3K27me3 Methylation activity of EZH2 facilitate heterochromatin formation thereby silences gene function which is important for development differentiation and cell fate determination
Accumulating studies have proved that EZH2 dysregulation is involved in human cancers EZH2 may have a dual role in cancer development acting as a tumour suppressor or an oncogene depending on the type of cancer Overexpression of EZH2 was observed in numerous solid tumours and targeting EZH2 can cause regression of carcinogenesis
EZH2 inactivation medicated by mutation or under-expression in myelo-dysplastic syndromes MDS or myeloproliferative neoplasms MPN can contribute to disease pathogenesis and is associated with a poor prognosis In AML EZH2 dysregulation caused by mutation and under-expression may act as potential biomarkers predicting prognosis and guiding the treatment choice between transplantation and chemotherapy EZH2 was found to have tumor suppressive and oncogenic functions in different phases of AML
However it remains to be defined whether deregulation of various PRC2-associated partners is also involved in malignancy development
PHF 19 PHD finger protein 19 a polycomb-like member of PRC2 cofactors acts as a critical mediator of tumorigenesis PHF 19 located in chromosome 9q332 encodes a member of the polycomb group PcG of proteins that functions by maintaining repressive transcriptional states of many developmental regulatory genes
PHF19 has been shown to be a major modulator of histone methylation thereby regulating transcriptional chromatin activity PHF19 directly recruits the polycomb repressive complex 2 PRC2 via binding to H3K36me3 and leads to activation of Enhancer of Zeste Homolog 2 EZH2 as enzymatic subunit of PRC2 thereby resulting in tri-methylation of H3K27 Previous studies confirmed that PHF19 is dysregulated in several types of cancer resulting in the derepression of PRC2 target genes and can be used as a marker of aggressive disease
To date there is no published data about role of both PHF19 and EZH2 in AML So this study was designed to explain unexplored critical oncogenic pathway of AML in which PHF19 pattern of expression and EZH2 gene deletion promote malignant progression and detect their prognostic role
Aim of the work
1 To detect pattern of expression of PHF19 gene by polymerase chain reaction PCR and EZH2 gene deletion by Fluorescence in situ Hybridization FISH in newly diagnosed AML patients
2 To study the association between expression PHF19 gene and EZH2 gene deletion in AML patients
3 Evaluation of the role of EZH2 and PHF19 genes as predictor markers of AML patient outcome
The etiological agent and pathogenesis of AML are not entirely clear only few AML cases can be accurately classified through traditional cellular morphological classification Thus it is very difficult to judge the disease condition and predict prognosis Improper expression of specific genes is a common finding in AML and may induce clinically relevant biological subsets Cytogenetic abnormalities and molecular alterations provide the most powerful prognostic information in AML Consequently identification of novel biomarkers which could predict outcome or guide treatment choice will make more contribution to the clinical management of AML
Gene repression is the deactivation of an active gene that causes shut down of transcription and it represents a powerful tool in controlling gene expression in order to prevent the metabolic dysregulation during the development or the differentiation program Polycomb repressive complex 2 PRC2 is the sole enzymatic complex capable of establishing gene-repression through high-degree methylation of histone H3 at lysine 27 H3K27 therefore it plays critical roles in regulation of normal hematopoiesis Enhancer of Zeste Homolog 2 EZH2 gene is the catalytic subunit of PRC2 located on chromosome 7q361 EZH2 gene encode EZH2 methyltransferase which mediates transcriptional inactivation through trimethylation of lysine 27 of histone H3 H3K27me3 Methylation activity of EZH2 facilitate heterochromatin formation thereby silences gene function which is important for development differentiation and cell fate determination
Accumulating studies have proved that EZH2 dysregulation is involved in human cancers EZH2 may have a dual role in cancer development acting as a tumour suppressor or an oncogene depending on the type of cancer Overexpression of EZH2 was observed in numerous solid tumours and targeting EZH2 can cause regression of carcinogenesis
EZH2 inactivation medicated by mutation or under-expression in myelo-dysplastic syndromes MDS or myeloproliferative neoplasms MPN can contribute to disease pathogenesis and is associated with a poor prognosis In AML EZH2 dysregulation caused by mutation and under-expression may act as potential biomarkers predicting prognosis and guiding the treatment choice between transplantation and chemotherapy EZH2 was found to have tumor suppressive and oncogenic functions in different phases of AML
However it remains to be defined whether deregulation of various PRC2-associated partners is also involved in malignancy development
PHF 19 PHD finger protein 19 a polycomb-like member of PRC2 cofactors acts as a critical mediator of tumorigenesis PHF 19 located in chromosome 9q332 encodes a member of the polycomb group PcG of proteins that functions by maintaining repressive transcriptional states of many developmental regulatory genes
PHF19 has been shown to be a major modulator of histone methylation thereby regulating transcriptional chromatin activity PHF19 directly recruits the polycomb repressive complex 2 PRC2 via binding to H3K36me3 and leads to activation of Enhancer of Zeste Homolog 2 EZH2 as enzymatic subunit of PRC2 thereby resulting in tri-methylation of H3K27 Previous studies confirmed that PHF19 is dysregulated in several types of cancer resulting in the derepression of PRC2 target genes and can be used as a marker of aggressive disease
To date there is no published data about role of both PHF19 and EZH2 in AML So this study was designed to explain unexplored critical oncogenic pathway of AML in which PHF19 pattern of expression and EZH2 gene deletion promote malignant progression and detect their prognostic role
Aim of the work
1 To detect pattern of expression of PHF19 gene by polymerase chain reaction PCR and EZH2 gene deletion by Fluorescence in situ Hybridization FISH in newly diagnosed AML patients
2 To study the association between expression PHF19 gene and EZH2 gene deletion in AML patients
3 Evaluation of the role of EZH2 and PHF19 genes as predictor markers of AML patient outcome
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