Genetic analysis of familial acute myeloid leukemia and myelodysplastic syndromes

Next Generation Sequencing (NGS) Approach to Study Known and New Germline Mutations in Familial Acute Myeloid Leukemia and Myelodisplastic Syndromes

This study is trying to find out if there are specific genetic changes in families with a history of acute myeloid leukemia or myelodysplastic syndromes to help understand how these conditions can be passed down.

Quick facts

• Study type: Observational
• Enrollment: 20 (estimated)
• Sex: All
• Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Academic / other)
• Locations: 1 site (Brescia)
• Trial ID: NCT03058588 on ClinicalTrials.gov

What this trial studies

This study aims to identify genetic mutations in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who have a family history of these conditions. Using next generation sequencing (NGS), researchers will screen both affected and unaffected family members for known and unknown mutations associated with these diseases. The study will involve both retrospective and prospective analyses, including gene panel deep sequencing and whole exome sequencing if necessary. The goal is to better understand the hereditary aspects of these malignancies and potentially identify new genetic predispositions.

Who should consider this trial

Good fit: Ideal candidates include patients diagnosed with AML or MDS who have a first- or second-degree relative with similar conditions or related lymphoproliferative disorders.

Not a fit: Patients without a familial history of AML, MDS, or related malignancies are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved genetic screening and risk assessment for families affected by AML and MDS.

How similar studies have performed: Previous studies utilizing genetic sequencing in familial cancer syndromes have shown promise, indicating that this approach may yield valuable insights.

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

Where this trial is running

Brescia

• Chair of Hematology and Bone marrow Transplant Unit — Brescia, Italy (Recruiting)

Study contacts

• Principal investigator: Domenico Russo, MD — Chair of Hematology
• Study coordinator: Domenico Russo, MD

Conditions Leukemia