Details

Autor(en) / Beteiligte

• Sébert, Marie
• Passet, Marie
• Raimbault, Anna
• Rahmé, Ramy
• Raffoux, Emmanuel
• Sicre de Fontbrune, Flore
• Cerrano, Marco
• Quentin, Samuel
• Vasquez, Nadia
• Da Costa, Mélanie
• Boissel, Nicolas
• Dombret, Hervé
• Peffault de Latour, Régis
• Socié, Gérard
• Itzykson, Raphaël
• Fenaux, Pierre
• Soulier, Jean
• Adès, Lionel
• Clappier, Emmanuelle

Titel

Germline DDX41 mutations define a significant entity within adult MDS/AML patients

Ist Teil von

• Blood, 2019-10, Vol.134 (17), p.1441-1444

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Germline DDX41 mutations are involved in familial myelodysplastic syndromes (MDSs) and acute myeloid leukemias (AMLs). We analyzed the prevalence and characteristics of DDX41-related myeloid malignancies in an unselected cohort of 1385 patients with MDS or AML. Using targeted next-generation sequencing, we identified 28 different germline DDX41 variants in 43 unrelated patients, which we classified as causal (n = 21) or unknown significance (n = 7) variants. We focused on the 33 patients having causal variants, representing 2.4% of our cohort. The median age was 69 years; most patients were men (79%). Only 9 patients (27%) had a family history of hematological malignancy, and 15 (46%) had a personal history of cytopenia years before MDS/AML diagnosis. Most patients had a normal karyotype (85%), and the most frequent somatic alteration was a second DDX41 mutation (79%). High-risk DDX41 MDS/AML patients treated with intensive chemotherapy (n = 9) or azacitidine (n = 11) had an overall response rate of 100% or 73%, respectively, with a median overall survival of 5.2 years. Our study highlights that germline DDX41 mutations are relatively common in adult MDS/AML, often without known family history, arguing for systematic screening. Salient features of DDX41-related myeloid malignancies include male preponderance, frequent preexisting cytopenia, additional somatic DDX41 mutation, and relatively good outcome. •Germline DDX41 mutations are found in a significant proportion of sporadic MDS/AML patients.•Patients with DDX41-related MDS/AML have a relatively favorable outcome. [Display omitted]