Ignite Creation Date:
2024-05-06 @ 12:58 PM
Last Modification Date:
2024-10-26 @ 1:06 PM
Study NCT ID:
NCT03894852
Status:
COMPLETED
Last Update Posted:
2020-05-19
First Post:
2019-03-27
Brief Title:
SRSF2 Gene Mutation in Patients With t-MDSAML
Sponsor:
Zeinab Albadry Mohammed Zahran
Organization:
Assiut University
Study Overview
Official Title:
SRSF2 Gene Mutation in Patients With Therapy Related Myelodysplastic Syndromes Acute Myeloid Leukemia
Status:
COMPLETED
Status Verified Date:
2020-05
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:
To detect SRSF2 gene mutation by polymerase chain reaction PCR in the two types of t-MDSAML which recognized in the WHO classification
Association between SRSF2 gene mutation and the presence of other cytogenetic abnormalities in the two types of t-MDSAML which recognized in the WHO classification eg Loss of chromosome 7 or del7q del5q isochromosome 17q recurrent balanced chromosomal translocations involving chromosomal segments 11q23 KMT2A previously called MLL or 21q221 RUNX1 and PML-RARA
Relationship between SRSF2 gene mutation and cumulative dose dose intensity time of exposure and prognostic criteria disease free survival overall survival and disease course
Association between SRSF2 gene mutation and the presence of other cytogenetic abnormalities in the two types of t-MDSAML which recognized in the WHO classification eg Loss of chromosome 7 or del7q del5q isochromosome 17q recurrent balanced chromosomal translocations involving chromosomal segments 11q23 KMT2A previously called MLL or 21q221 RUNX1 and PML-RARA
Relationship between SRSF2 gene mutation and cumulative dose dose intensity time of exposure and prognostic criteria disease free survival overall survival and disease course
Detailed Description:
Therapy-related myeloid neoplasms t-MNs are a group of hematologic diseases that arise after chemotherapy andor radiation therapy for a previous cancer or rarely autoimmune diseases
The revised 2016 World Heath Organization WHO classification defines t-MN as a subgroup of acute myeloid leukemia AML comprising myelodysplastic syndrome t-MDS acute myeloid leukemia t-AML and myelodysplasticmyeloproliferative neoplasms t-MDSMPN
Two forms of t-MN have been recognized Alkylating agentradiation-related t-MN usually appears 4 to 7 years which is frequently associated with unbalanced chromosomal abnormalities involving chromosomes 5 andor 7 as well mutations or loss of TP53 tumor protein 53
In contrast a combination of different topoisomerase II inhibitor-related t-MNs is associated with a high incidence of recurrent balanced translocations involving chromosomal segments 11q23 KMT2A 21q22 RUNX1 and PML-RARA 1
T-MNs are characterized by a subset of molecular mutations including SRSF2 SF3B1 U2AF1 ZRSR2 ASXL1 STAG2 and TP53
RNA splicing is a process that produces mature mRNAs by excising introns and splicing exons from pre-messenger RNA The spliceosome mutations induce an abnormally spliced mRNA species and compromising hematopoiesis
One of the potential candidate genes involved in the RNA splicing pathway is serine and arginine rich splicing factor 2 SRSF2 SRSF2 located on chromosome 17q251 and plays a role in preventing exon skipping confirming the accuracy of splicing and regulating alternative pre-mRNA splicing Many studies have already reported the potential prognostic value of SRSF2 mutations which have an adverse prognostic impact on survival and disease progression
Somatic mutations recently identified in patients with de novo AML and MDS such as those of epigenetic regulators spliceosome machinery and SETBP1 are rare with the exception of SRSF2
TP53 mutations have been associated to the occurrence of cytogenetic abnormalities and poor response to chemotherapy that are typical of t-MN
On the other hand several studies have shown that the presence of isochromosome 17q i17q abnormality is associated with wild-type TP53 and mutations in SETBP1 and SRSF2
Also somatic loss of one copy of the long arm of chromosome 7 del7q is associated with unfavorable prognosis and can co-occur with the SRSF2 mutation in patients with MDS and AML
The revised 2016 World Heath Organization WHO classification defines t-MN as a subgroup of acute myeloid leukemia AML comprising myelodysplastic syndrome t-MDS acute myeloid leukemia t-AML and myelodysplasticmyeloproliferative neoplasms t-MDSMPN
Two forms of t-MN have been recognized Alkylating agentradiation-related t-MN usually appears 4 to 7 years which is frequently associated with unbalanced chromosomal abnormalities involving chromosomes 5 andor 7 as well mutations or loss of TP53 tumor protein 53
In contrast a combination of different topoisomerase II inhibitor-related t-MNs is associated with a high incidence of recurrent balanced translocations involving chromosomal segments 11q23 KMT2A 21q22 RUNX1 and PML-RARA 1
T-MNs are characterized by a subset of molecular mutations including SRSF2 SF3B1 U2AF1 ZRSR2 ASXL1 STAG2 and TP53
RNA splicing is a process that produces mature mRNAs by excising introns and splicing exons from pre-messenger RNA The spliceosome mutations induce an abnormally spliced mRNA species and compromising hematopoiesis
One of the potential candidate genes involved in the RNA splicing pathway is serine and arginine rich splicing factor 2 SRSF2 SRSF2 located on chromosome 17q251 and plays a role in preventing exon skipping confirming the accuracy of splicing and regulating alternative pre-mRNA splicing Many studies have already reported the potential prognostic value of SRSF2 mutations which have an adverse prognostic impact on survival and disease progression
Somatic mutations recently identified in patients with de novo AML and MDS such as those of epigenetic regulators spliceosome machinery and SETBP1 are rare with the exception of SRSF2
TP53 mutations have been associated to the occurrence of cytogenetic abnormalities and poor response to chemotherapy that are typical of t-MN
On the other hand several studies have shown that the presence of isochromosome 17q i17q abnormality is associated with wild-type TP53 and mutations in SETBP1 and SRSF2
Also somatic loss of one copy of the long arm of chromosome 7 del7q is associated with unfavorable prognosis and can co-occur with the SRSF2 mutation in patients with MDS and AML
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