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Thromb Haemost 2009; 102(01): 90-96
DOI: 10.1160/TH09-01-0068
Platelets and Blood Cells
Schattauer GmbH

Megakaryocytes of patients with MYH9-related thrombocytopenia present an altered proplatelet formation

Alessandro Pecci
1   Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
,
Alessandro Malara
2   Department of Biochemistry, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
,
Stefania Badalucco
2   Department of Biochemistry, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
,
Valeria Bozzi
1   Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
,
Mauro Torti
2   Department of Biochemistry, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
,
Carlo L. Balduini
1   Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
,
Alessandra Balduini
2   Department of Biochemistry, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
› Author AffiliationsFinancial support: This study was supported by grants from the Telethon Foundation (GGP06177) (CLB, MT), the Italian Ministero della Salute (CLB), the Italian Istituto Superiore di Sanità (CLB), the Cariplo Foudation (AB), and the Banca del Monte di Lombardia Foundation (AB).
Further Information

Publication History

Received: 30 January 2009

Accepted after minor revision: 17 April 2009

Publication Date:
24 November 2017 (online)

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Summary

MYH9-related disease (MYH9-RD) is an autosomal-dominant thrombocytopenia caused by mutations of MYH9, the gene for the heavy chain of myosin-IIA. Pathogenesis of thrombocytopenia of MYH9-RD is unknown. Recent studies in mice demonstrated that myosin-IIA is an inhibitor of proplatelet formation (PPF), and suggested that it could be involved in the suppression of PPF exerted by megakaryocyte adhesion to type I collagen, which regulates the timing of platelet release within bone marrow. However, the consequences on PPF of the heterozygous mutations causative of the MYH9-RD have never been investigated. We studied the in-vitro PPF by megakaryocytes obtained from four patients carrying the p.D1424N or the p.R1933X mutations. We demonstrated that MYH9-RD megakaryocytes completely lose the physiologic suppression of proplatelet extension exerted by interaction with type I collagen, thus supporting the hypothesis that a premature platelet release within bone marrow contributes to pathogenesis of MYH9-related thrombocytopenia. Moreover, proplatelets extended by MYH9-RD megakaryocytes presented a significant defect in branching in secondary processes (p=0.001) and formed a significantly lower number of proplatelet tips (p=0.005). Since platelets are assembled at the level of proplatelet tips, this defect could further contribute to pathogenesis of thrombocytopenia of MYH9-RD patients.

Keywords

Inherited thrombocytopenia - MYH9-related disease - myosin-IIA - proplatelet formation
 

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