Next Generation Sequencing (NGS) in Familial Acute Myeloid Leukemia and Myelodisplastic Syndromes

Last updated: December 7, 2024
Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Overall Status: Active - Recruiting

Phase

N/A

Condition

Leukemia

Treatment

Analysis with molecular biology

Clinical Study ID

NCT03058588
NEXT-FAMLY 1016
  • All Genders

Study Summary

The aim of this study is to look for predisposing mutations in patients and relatives affected by AML and MDS with familial history of myeloid or, less frequently, lymphoid malignancies. Taking advantage of a next generation sequencing (NGS) platform, screening for known and unknown mutations potentially associated with the disease will be done. The screening will be performed on affected and unaffected family members, in order to outline new pedigrees that either validate previous findings or constitute novel discoveries.

Eligibility Criteria

Inclusion

Inclusion criteria:

Any patient with acute myeloid leukemia (AML) or Myelodisplastic Syndrome (MDS) with:

  1. a first- or second-degree relative with Acute leukemia or MDS or other myeloidmalignancies

  2. a first- or second-degree relative with Lymphoproliferative neoplasms

  3. or with clinical features that resemble one of the familial MDS/AML predispositionsyndromes:

  • History of thrombocytopenia and/or a clinical bleeding propensity (as in RUNX1,ANKRD26 or ETV6 germline mutations)

  • Abnormal nails or skin pigmentation, oral leukoplakia, idiopathic pulmonaryfibrosis, unexplained liver disease (as in TERT and TERC germline mutations)

  • Lymphedema, atypical infections, immune deficiencies (as in GATA2 germlinemutations)

Exclusion

Exclusion Criteria:

  1. any diagnosis other than acute myeloid leukemia (AML) or Myelodisplastic Syndrome (MDS);

  2. acute myeloid leukemia (AML) or Myelodisplastic Syndrome (MDS) without a first- orsecond-degree relative with Acute leukemia or MDS or other myeloid malignancies orwithout a first- or second-degree relative with Lymphoproliferative neoplasms orwith clinical features that resemble one of the familial MDS/AML predispositionsyndromes;

  3. unability to sign the informed consent

Study Design

Total Participants: 20
Treatment Group(s): 1
Primary Treatment: Analysis with molecular biology
Phase:
Study Start date:
February 09, 2017
Estimated Completion Date:
December 31, 2024

Study Description

Patients with a diagnosis of AML or MDS with at least one relative affected by AL/MDS or, secondly, lymphoproliferative disorders, will be enrolled into the study, and will be referred to as the index case. The analysis will be performed both retrospectively and prospectively. A gene panel deep sequencing (GPDS) of the tumor DNA from peripheral blood of the index case at diagnosis will be performed in order to identify mutations in a number of genes known to be associated to myeloid malignancies, mainly: ASXL1, BCOR, NRAS, TP53, RUNX1, CEBPA, FLT3, EZH2, IDH1, IDH2, NPM1, DNMT3A, TET2, CBL, KRAS, ETV6, SF3B1, SRSF2, U2AF1, ZRSR2, GATA2, TERT, TERC, SRP72, and ANKRD26.

In case none of the known mutations is found by the GPDS, whole exome sequencing (WES) will be performed as second step on the tumor cells of the index case.

When one or multiple somatic mutations are found, a Sanger Sequencing (SS) on germline DNA from epithelial buccal cells of the index cases and affected relatives will be performed for the screening of the same somatic leukemic mutations on germline DNA. If the index case and affected relatives share the same mutations on the germline, the same germline mutations will be checked by SS in the unaffected family members.

Connect with a study center

  • Chair of Hematology and Bone marrow Transplant Unit

    Brescia, 25123
    Italy

    Active - Recruiting

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