SRSF2 Gene Mutation in Patients With t-MDS/AML

NCT03894852 | Completed

• 1 other identifier: SRSF2 mutation in t-MDS/AML
• Study Type: observational
• Target: 139
• Locations: 1 country
• Sites: 2

Brief Summary

• 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).

Conditions

Therapy Related Myelodysplastic Syndrome and Therapy Related Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• SRSF2 gene mutation detection in t-MDS/AML.

  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 Outcomes (1)

• Cytogenetic analysis (FISH) of patient with t-MDS/AML.

  about 2 years

Study Arms (2)

AML

cases with denovo AML and t-AML

Diagnostic Test: PCR and cytogenetics

MDS

cases with denovo MDS and t-MDS

Diagnostic Test: PCR and cytogenetics

Interventions

PCR and cytogenetics DIAGNOSTIC_TEST

detection of SRSF2 gene mutation and cytogenetic studies

AML; MDS

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Zeinab Albadry Mohammed Zahran: lead

Study Sites (2)

Assiut

Asyut, 71515, Egypt

Location

Zeinab Albadry Mohammed Zahran

Asyut, 71515, Egypt

Location

Related Publications (12)

• Fianchi L, Criscuolo M, Fabiani E, Falconi G, Maraglino AME, Voso MT, Pagano L. Therapy-related myeloid neoplasms: clinical perspectives. Onco Targets Ther. 2018 Sep 17;11:5909-5915. doi: 10.2147/OTT.S101333. eCollection 2018.

  PMID: 30271175 BACKGROUND

• Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. doi: 10.1182/blood-2016-03-643544. Epub 2016 Apr 11.

  PMID: 27069254 BACKGROUND

• Sella T, Stone RM. The impact of new drugs for breast and ovarian cancer on the occurrence of therapy-related myeloid neoplasms: Understanding the baseline incidence. Gynecol Oncol. 2018 Nov;151(2):187-189. doi: 10.1016/j.ygyno.2018.10.013. No abstract available.

  PMID: 30384959 BACKGROUND

• Hoskins AA, Moore MJ. The spliceosome: a flexible, reversible macromolecular machine. Trends Biochem Sci. 2012 May;37(5):179-88. doi: 10.1016/j.tibs.2012.02.009. Epub 2012 Apr 3.

  PMID: 22480731 BACKGROUND

• Boultwood J, Dolatshad H, Varanasi SS, Yip BH, Pellagatti A. The role of splicing factor mutations in the pathogenesis of the myelodysplastic syndromes. Adv Biol Regul. 2014 Jan;54:153-61. doi: 10.1016/j.jbior.2013.09.005. Epub 2013 Sep 15.

  PMID: 24080589 BACKGROUND

• Maciejewski JP, Padgett RA. Defects in spliceosomal machinery: a new pathway of leukaemogenesis. Br J Haematol. 2012 Jul;158(2):165-173. doi: 10.1111/j.1365-2141.2012.09158.x. Epub 2012 May 18.

  PMID: 22594801 BACKGROUND

• Armstrong RN, Steeples V, Singh S, Sanchi A, Boultwood J, Pellagatti A. Splicing factor mutations in the myelodysplastic syndromes: target genes and therapeutic approaches. Adv Biol Regul. 2018 Jan;67:13-29. doi: 10.1016/j.jbior.2017.09.008. Epub 2017 Sep 22.

  PMID: 28986033 BACKGROUND

• Fabiani E, Falconi G, Fianchi L, Criscuolo M, Ottone T, Cicconi L, Hohaus S, Sica S, Postorino M, Neri A, Lionetti M, Leone G, Lo-Coco F, Voso MT. Clonal evolution in therapy-related neoplasms. Oncotarget. 2017 Feb 14;8(7):12031-12040. doi: 10.18632/oncotarget.14509.

  PMID: 28076841 BACKGROUND

• Visconte V, Tabarroki A, Zhang L, Hasrouni E, Gerace C, Frum R, Ai J, Advani AS, Duong HK, Kalaycio M, Saunthararajah Y, Sekeres MA, His ED, Shetty S, Rogers HJ, Tiu RV. Clinicopathologic and molecular characterization of myeloid neoplasms harboring isochromosome 17(q10). Am J Hematol. 2014 Aug;89(8):862. doi: 10.1002/ajh.23755. Epub 2014 May 16. No abstract available.

  PMID: 24796269 BACKGROUND

• Meggendorfer M, Bacher U, Alpermann T, Haferlach C, Kern W, Gambacorti-Passerini C, Haferlach T, Schnittger S. SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations. Leukemia. 2013 Sep;27(9):1852-60. doi: 10.1038/leu.2013.133. Epub 2013 Apr 30.

  PMID: 23628959 BACKGROUND

• Papapetrou EP. Patient-derived induced pluripotent stem cells in cancer research and precision oncology. Nat Med. 2016 Dec 6;22(12):1392-1401. doi: 10.1038/nm.4238.

  PMID: 27923030 BACKGROUND

• Kanagal-Shamanna R, Bueso-Ramos CE, Barkoh B, Lu G, Wang S, Garcia-Manero G, Vadhan-Raj S, Hoehn D, Medeiros LJ, Yin CC. Myeloid neoplasms with isolated isochromosome 17q represent a clinicopathologic entity associated with myelodysplastic/myeloproliferative features, a high risk of leukemic transformation, and wild-type TP53. Cancer. 2012 Jun 1;118(11):2879-88. doi: 10.1002/cncr.26537. Epub 2011 Oct 28.

  PMID: 22038701 BACKGROUND

Study Officials

• Zeinab Abdel-Aal Jad Elrab, Professor

  Clinical pathology Department, Faculty of Medicine, Assiut University

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant lecturer,Clinical Pathology Departement,Faculty of Medicine, Assiut University

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: March 29, 2019
• Study Start: June 2, 2019
• Primary Completion: December 29, 2019
• Study Completion: April 29, 2020
• Last Updated: May 19, 2020

Record last verified: 2020-05

Locations

EG (2)