Megakaryocyte apoptosis in immune thrombocytopenia

Abstract

The mechanisms of platelet underproduction in immune thrombocytopenia (ITP) remain unknown. While the number of megakaryocytes is normal or increased in ITP bone marrow, further studies of megakaryocyte integrity are needed. Megakaryocytes are responsible for the production of platelets in the bone marrow, and they are possible targets of immune-mediated injury in ITP. Since the biological process of megakaryocyte apoptosis impacts platelet production, we investigated megakaryocyte DNA fragmentation as a marker of apoptosis from ITP bone marrow biopsies. Archived bone marrow biopsy specimens from ITP patients, bone marrow specimens from controls with normal platelet counts, and bone marrow specimens from thrombocytopenic controls with myelodysplastic syndrome (MDS) were evaluated. Sections were stained with anti-CD61 for megakaryocyte enumeration, and terminal deoxynucleotidyl transferase dUTP nick-end labeling was used as an apoptotic indicator. In ITP patients, megakaryocyte apoptosis was reduced compared to nonthrombocytopenic controls. Megakaryocyte apoptosis was similarly reduced in thrombocytopenic patients with MDS. These results suggest a link between megakaryocyte apoptosis and platelet production.

Keywords:

• Apoptosis
• autoimmune disease
• bone marrow pathology
• ITP
• megakaryocytes

Acknowledgments

I Nazy holds a McMaster University Internal Career Research Award from the Department of Medicine. DM Arnold holds the JG Kelton Chair in Translational Research from McMaster University.

Declaration of Interest

The authors report no declarations of interest.

Additional information

Funding

This study was funded by the Canadian Institute for Health Research (CIHR Operating Grant #89897). Program funding was provided by Canadian Blood Services, and the federal government of Canada (Health Canada).