Same shades of gray but different protein compositions

Maaike van Bergen, theme Cancer development and immune defence, and other researchers, published in Blood about specific proteome changes in platelets from individuals with GATA1-, GFI1B- and RUNX1-linked bleeding disorders.

A subset of inherited bleeding disorders is caused by mutations in the related transcription factors GATA1, GFI1B and RUNX1. Platelets from individuals with these mutations appear grayish in blood smear staining due to a lack of granules that are important for blood clot formation. As GATA1, GFI1B and RUNX1 interact at the protein and genetic level it has been proposed that they regulate similar gene programs.

Maaike van Bergen from the Van der Reijden group, Laboratory of Hematology, addressed this hypothesis by proteomic profiling of gray platelets from bleeding disorder cases with GATA1, GFI1B or RUNX1 mutations. Platelet proteomes were compared to those from healthy donors. In mutant derived platelets, a significant reduction of numerous proteins assigned to platelet function, hemostasis and granule biology was observed. Unexpectedly, none of the up- or downmodulated proteins were shared in common. These data indicate that mutant GATA1, GFI1B, and RUNX1 affect platelet proteomes in distinct, non-overlapping manners, despite the large overlap in platelet phenotypes. This work provides a basis to further our understanding of platelet biology and how mutant transcription factors deregulate platelet proteomes differently.

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