SRSF2 Gene Mutation in Patients With t-MDS/AML

May 17, 2020 updated by: Zeinab Albadry Mohammed Zahran

SRSF2 Gene Mutation in Patients With Therapy Related Myelodysplastic Syndromes / Acute Myeloid Leukemia

  • To detect SRSF2 gene mutation by polymerase chain reaction (PCR) in the two types of t-MDS/AML which recognized in the WHO classification.
  • Association between SRSF2 gene mutation and the presence of other cytogenetic abnormalities in the two types of t-MDS/AML which recognized in the WHO classification, e.g. (Loss of chromosome 7 or del(7q), del(5q), isochromosome 17q, recurrent balanced chromosomal translocations involving chromosomal segments 11q23 (KMT2A, previously called MLL) or 21q22.1 (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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Therapy-related myeloid neoplasms (t-MNs) are a group of hematologic diseases that arise after chemotherapy and/or 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 myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN) .

Two forms of t-MN have been recognized. Alkylating agent/radiation-related t-MN usually appears 4 to 7 years, which is frequently associated with unbalanced chromosomal abnormalities involving chromosomes 5 and/or 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 17q25.1, 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 i(17q) 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 del(7q) is associated with unfavorable prognosis and can co-occur with the SRSF2 mutation in patients with MDS and AML.

Study Type

Observational

Enrollment (Actual)

139

Contacts and Locations

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

Study Locations

  • Egypt
      • Assiut, Egypt, 71515
        • Assiut
      • Assiut, Egypt, 71515
        • Zeinab Albadry Mohammed Zahran

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

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Cases diagnosed therapy related MDS/AML admitted to department of Clinical Pathology, in the south Egypt cancer institute and Assiut University Hospital.

Description

Inclusion Criteria:

  • Patients with myelodysplastic syndromes (MDS), who fulfill the WHO criteria.
  • Patients with acute myeloid leukemia (AML), who fulfill the WHO criteria.
  • Patients must start therapy (cytotoxic agents and/or ionizing radiotherapy) before beginning of the study, with a documented history of a benign or malignant condition for which they had received therapy prior to the diagnosis of MDS or AML.

Exclusion Criteria:

  • Patients not fulfill the WHO criteria for diagnosis of MDS and AML.

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

  • Observational Models: Other
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
AML
cases with denovo AML and t-AML
Diagnostic test: PCR and cytogenetics
detection of SRSF2 gene mutation and cytogenetic studies
MDS
cases with denovo MDS and t-MDS
Diagnostic test: PCR and cytogenetics
detection of SRSF2 gene mutation and cytogenetic studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SRSF2 gene mutation detection in t-MDS/AML.
Time Frame: about 2 years
Detect SRSF2 gene mutation by polymerase chain reaction (PCR) in the two types of t-MDS/AML which recognized in the WHO classification.
about 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cytogenetic analysis (FISH) of patient with t-MDS/AML.
Time Frame: about 2 years

Cytogenetic analysis (FISH), e.g. (Loss of chromosome 7 or del(7q), del(5q), lsochromosome 17q, recurrent balanced chromosomal translocations involving chromosomal segments 11q23 (KMT2A, previously called MLL) or 21q22.1 (RUNX1), and PML-RARA) in the two types of t-MDS/AML which recognized in the WHO classification.

.
about 2 years

Collaborators and Investigators

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

Sponsor

Zeinab Albadry Mohammed Zahran

Investigators

  • Study Director: Zeinab Abdel-Aal Jad Elrab, Professor, Clinical pathology Department, Faculty of Medicine, Assiut University
  • Principal Investigator: Sahar Abdullah El-Gammal, Assistant Professor, Clinical pathology Department, Faculty of Medicine, Assiut University
  • Principal Investigator: Madleen Adel Attia, Assistant Professor, Clinical pathology Department, Faculty of Medicine, 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 (Actual)

June 2, 2019

Primary Completion (Actual)

December 29, 2019

Study Completion (Actual)

April 29, 2020

Study Registration Dates

First Submitted

March 27, 2019

First Submitted That Met QC Criteria

March 27, 2019

First Posted (Actual)

March 29, 2019

Study Record Updates

Last Update Posted (Actual)

May 19, 2020

Last Update Submitted That Met QC Criteria

May 17, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SRSF2 mutation in t-MDS/AML

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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