Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

EUropean PLAtelet NEtwork for studying physiopathology of two inherited thrombocytopenias, THC2 and MYH9-RD, characterized by genetic alterations of RUNX1-target genes

Project Coordinator

IRCCS Policlinico San Matteo Foundation


Manuela Germeshausen Medizinische Hochschule Hannover Hannover, Germany
Hana Raslova INSERM U1016 Villejuif, France

The aim of this project is to identify the pathogenetic mechanisms of two inherited thrombocytopenias both described for the first time by partner 1. The first, MYH9-related disease, is characterized by macrothrombocytopenia and mutations in MYH9 gene. MYH9 has been identified as a direct RUNX1 target by partner 2. However, in FPD/AML patients with RUNX1 mutations, the level of MYH9 is decreased of a half and no macroplatelets are detected suggesting that the MYH9 mutants in MYH9-RD acquired rather a new function. The second thrombocytopenia is THC2. THC2 is characterized by normal platelet size and by mutations in 5’UTR region of ANKRD26 gene. Recently we have demonstrated (partners 1 and 2) that these mutations abolished RUNX1 and FLI1 binding necessary to down-regulate ANKRD26 during megakaryopoiesis in THC2 patients. The transnational collaboration will permit us to perform an exhaustive and thus statistically significant study of the precise mechanisms of the physiopathology of these two thrombocytopenias in large cohorts of patients. In particular, it will allow us to: 1. describe the newly acquired function of MYH9 mutants in MYH9-RD, 2. understand how maintained expression of ANKRD26 in megakaryocytes induces the dysmegakaryopoiesis, 3. show if the new structures “PaCS” identified in ANKRD26 mutated patients are linked to the transformation process, 4. establish a link between ANKRD26 mutations and the predisposition to hematological malignancies, 5. establish a rapid diagnostic test for THC2, 6. propose rational treatment strategies for THC2 and MYH9-RD.

E-Rare 2012 - Created by Toussaint Biger