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

Alessandro Pecci; Alessandro Malara; Stefania Badalucco; Valeria Bozzi; Mauro Torti; Carlo L. Balduini; Alessandra Balduini

doi:10.1160/TH09-01-0068

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

,

Alessandro Malara

²Department of Biochemistry, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

,

Stefania Badalucco

²Department of Biochemistry, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

,

Valeria Bozzi

¹Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

,

Mauro Torti

²Department of Biochemistry, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

,

Carlo L. Balduini

¹Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

,

Alessandra Balduini

²Department of Biochemistry, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

› Author Affiliations

Abstract

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

Full Text

References

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