Fiche publication
Date publication
mai 2018
Journal
Haematologica
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LIOURE Bruno
Tous les auteurs :
Donadieu J, Lamant M, Fieschi C, Sicre de Fontbrune F, Caye A, Ouachee M, Beaupain B, Bustamante J, Poirel HA, Isidor B, Van Den Neste E, Neel A, Nimubona S, Toutain F, Barlogis V, Schleinitz N, Leblanc T, Rohrlich P, Suarez F, Ranta D, Abou Chahla W, Bruno B, Terriou L, Francois S, Lioure B, Ahle G, Bachelerie F, Preudhomme C, Delabesse E, Cavé H, Bellanné-Chantelot C, Pasquet M,
Lien Pubmed
Résumé
Heterozygous germline GATA2 mutations strongly predispose to leukaemia, immunodeficiency, and/or lymphoedema. We now describe a series of 79 patients (53 families) diagnosed since 2011, compiling all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and haematological malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukaemia in patients with missense mutations (n=14/34) than in patients with nonsense or frameshift mutations (n=2/28). We also identify new features of the disease: acute lymphoblastic leukaemia, juvenile myelomonocytic leukaemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised IPSS score allowed a distinction to be made between a stable disease and haematological transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), haematopoietic stem-cell transplantation remains the best choice of treatment to avoid severe infectious and/or haematological complications. The timing of haematopoietic stem-cell transplantation remains difficult to determine, but the earlier it is performed, the better the outcome.
Référence
Haematologica. 2018 May 3;:
