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

NCT ID: NCT03058588

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-02-09
• Study Completion Date: 2025-12-31

Brief 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.

Detailed 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.

Conditions

Leukemia

Study Design

• Observational Model Type: FAMILY_BASED
• Study Time Perspective: PROSPECTIVE

Study Groups

Analysis with molecular biology

Any patient with acute leukemia or other myeloid malignancy AND

1. a first- or second-degree relative with acute leukemia or other myeloid malignancies

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

3. or with clinical features that resemble one of the familial myeloid malignancies predisposition syndromes

Analysis with molecular biology

Intervention Type: GENETIC

Molecular screening by next generation sequencing (NGS) platform, for known and unknown mutations potentially associated with the disease

Interventions

Analysis with molecular biology

Molecular screening by next generation sequencing (NGS) platform, for known and unknown mutations potentially associated with the disease

Intervention Type: GENETIC

Eligibility Criteria

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 myeloid malignancies

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

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

• 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 pulmonary fibrosis, unexplained liver disease (as in TERT and TERC germline mutations)
• Lymphedema, atypical infections, immune deficiencies (as in GATA2 germline mutations)

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- or second-degree relative with Acute leukemia or MDS or other myeloid malignancies or without a first- or second-degree relative with Lymphoproliferative neoplasms or with clinical features that resemble one of the familial MDS/AML predisposition syndromes;

3. unability to sign the informed consent

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

OTHER

Sponsor Role: lead

Responsible Party

Prof Domenico Russo

Full Professor of Hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Domenico Russo, MD

Role: PRINCIPAL_INVESTIGATOR

Chair of Hematology

Locations

Chair of Hematology and Bone marrow Transplant Unit

Brescia, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Domenico Russo, MD

Role: CONTACT

domenico.russo@unibs.it

0039303996811

Francesca Schieppati, MD

Role: CONTACT

fschieppati@gmail.com

0039303996811

Facility Contacts

Domenico Russo, MD

Role: primary

domenico.russo@unibs.it

Francesca Schieppati, MD

Role: backup

fschieppati@gmail.com

Other Identifiers

NEXT-FAMLY 1016

Identifier Type: -

Identifier Source: org_study_id