Haematological spectrum and genotype-phenotype correlations in nine unrelated families with RUNX1 mutations from the French network on inherited platelet disorders.

International audienceLess than 50 patients with FPD/AML (OMIM 601309) have been reported as of today and there may an underestimation. The purpose of this study was to describe the natural history, the haematological features and the genotype-phenotype correlations of this entity in order to, first, screen it better and earlier, before leukaemia occurrence and secondly to optimize appropriate monitoring and treatment, in particular when familial stem cell transplantation is considered.We have investigated 41 carriers of RUNX1 alteration belonging to nine unrelated French families with FPD/AML and two syndromic patients, registered in the French network on rare platelet disorders from 2005 to 2015.Five missense, one non-sense, three frameshift mutations and two large deletions involving several genes including RUNX1 were evidenced. The history of familial leukaemia was suggestive of FPD/AML in seven pedigrees, whereas an autosomal dominant pattern of lifelong thrombocytopenia was the clinical presentation of two. Additional syndromic features characterized two large sporadic deletions. Bleeding tendency was mild and thrombocytopenia moderate (>50 x10(9)/L), with normal platelet volume. A functional platelet defect consistent with a δ-granule release defect was found in ten patients regardless of the type of RUNX1 alteration. The incidence of haematological malignancies was higher when the mutated RUNX1 allele was likely to cause a dominant negative effect (19/34) in comparison with loss of function alleles (3/9). A normal platelet count does not rule out the diagnosis of FPD/AML, since the platelet count was found normal for three mutated subjects, a feature that has a direct impact in the search for a related donor in case of allogeneic haematopoietic stem cell transplantation.Platelet dysfunction suggestive of defective δ-granule release could be of values for the diagnosis of FPD/AML particularly when the clinical presentation is an autosomal dominant thrombocytopenia with normal platelet size in the absence of familial malignancies. The genotype-phenotype correlations might be helpful in genetic counselling and appropriate optimal therapeutic management

Biological Description of 109 Cases of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) from the French Network of BPDCN

WOS:000368021800069International audience55th Annual Meeting and Exposition of the American-Society-of-Hematology - New Orleans, LA 201

Biological Description of 109 Cases of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) from the French Network of BPDCN

WOS:000368021800069International audience55th Annual Meeting and Exposition of the American-Society-of-Hematology - New Orleans, LA 201

Spectrum of the Mutations in Bernard-Soulier Syndrome

Bernard-Soulier syndrome (BSS) is a rare autosomal recessive bleeding disorder characterized by defects of the GPIb-IX-V complex, a platelet receptor for von Willebrand factor (VWF). Most of the mutations identified in the genes encoding for the GP1BA (GPIbα), GP1BB (GPIbβ), and GP9 (GPIX) subunits prevent expression of the complex at the platelet membrane or more rarely its interaction with VWF. As a consequence, platelets are unable to adhere to the vascular subendothelium and agglutinate in response to ristocetin. In order to collect information on BSS patients, we established an International Consortium for the study of BSS, allowing us to enrol and genotype 132 families (56 previously unreported). With 79 additional families for which molecular data were gleaned from the literature, the 211 families characterized so far have mutations in the GP1BA (28%), GP1BB (28%), or GP9 (44%) genes. There is a wide spectrum of mutations with 112 different variants, including 22 novel alterations. Consistent with the rarity of the disease, 85% of the probands carry homozygous mutations with evidence of founder effects in some geographical areas. This overview provides the first global picture of the molecular basis of BSS and will lead to improve patient diagnosis and management.Fil: Savoia, Anna. Università degli Studi di Trieste; Italia. Istituto di Ricovero e Cura a Carattere Scientifico “Burlo Garofolo”; ItaliaFil: Kunishima, Shinji. National Hospital Organization Nagoya Medical Center; JapónFil: De Rocco, Daniela. Università degli Studi di Trieste; ItaliaFil: Zieger, Barbara. University Medical Center of Freiburg; AlemaniaFil: Rand, Margaret L.. Hospital for Sick Children; CanadáFil: Pujol Moix, Nuria. Universidad de Barcelona; España. Sant Pau Research Institute; EspañaFil: Caliskan, Umran. Necmettin Erbakan University; TurquíaFil: Tokgoz, Huseyin. Necmettin Erbakan University; TurquíaFil: Pecci, Alessandro. University of Pavia; ItaliaFil: Noris, Patrizia. University of Pavia; ItaliaFil: Srivastava, Alok. Christian Medical College; IndiaFil: Ward, Christopher. University of Sydney; Australia. Royal North Shore Hospital; AustraliaFil: Morel Kopp, Marie Christine. University of Sydney; Australia. Royal North Shore Hospital; AustraliaFil: Alessi, Marie Christine. Université Aix Marseille; FranciaFil: Bellucci, Sylvia. Hôpital Lariboisière; FranciaFil: Beurrier, Philippe. Centre Hospitalier Universitaire d’Angers; FranciaFil: de Maistre, Emmanuel. Hôpital du Bocage; FranciaFil: Favier, Rémi. Hôpital d'enfants A Trousseau; FranciaFil: Hézard, Nathalie. Hôpital Robert Debré; FranciaFil: Hurtaud Roux, Marie Françoise. Hôpital Robert Debré; FranciaFil: Latger Cannard, Véronique. Centre de Compétence des Pathologies Plaquettaires Nord-Est; FranciaFil: Lavenu Bombled, Cécile. Universite Paris Sud; FranciaFil: Proulle, Valérie. Universite Paris Sud; FranciaFil: Meunier, Sandrine. Unité d’Hémostase Clinique de Lyon; FranciaFil: Négrier, Claude. Hôpital Edouard Herriot; FranciaFil: Nurden, Alan. Institut de Rythmologie et Modélisation Cardiaque; FranciaFil: Randrianaivo, Hanitra. Centre Hospitalier Universitaire, Saint-Pierre; FranciaFil: Fabris, Fabrizio. Università di Padova; ItaliaFil: Platokouki, Helen. Children's Hospital. Haemophilia Centre/Haemostasis Unit “Aghia Sophia”; GreciaFil: Rosenberg, Nurit. Sheba Medical Center. Amalia Biron Research Institute of Thrombosis and Hemostasis; IsraelFil: HadjKacem, Basma. Sfax University; TúnezFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Karimi, Mehran. Shiraz University of Medical Sciences; IránFil: Balduini, Carlo L.. University of Pavia; ItaliaFil: Pastore, Annalisa. King's College London; Reino UnidoFil: Lanza, Francois. Université de Strasbourg; Franci