21 January 2019

Rinske van Oorschot from the Van der Reijden group (Laboratory Hematology, Dept Laboratory Medicine), theme Cancer development and immune defense, has published two papers on the transcription factor GFI1B in Haematologica.

Earlier work from the Van der Reijden group showed that an inherited GFI1B mutation severely disturbed the formation of megakaryocytes and their production of blood platelets. Together with the Dept of Molecular Biology, Radboud University and Sanquin Blood Supply, Amsterdam, Rinske now shows that mutant GFI1B functions in a dominant-negative manner by squelching the chromatin modifying CoREST complex, making it unavailable for wild type GFI1B1. Proteomics on megakaryocytes generated from patient-derived induced pluripotent stem cells identified a plethora of pathways regulated by GFI1B.

In another study, Rinske shows together with groups from Leuven, Belgium and Cambridge, U.K., the functional effects of new inherited GFI1B variants observed in cases with unexplained bleedings2. This work identifies novel important functional domains in GFI1B. Together, Rinske's studies shed important light on the function of GFI1B in the formation of platelets and bleeding disorders.
  1. Molecular mechanisms of bleeding disorder-associated GFI1BQ287* mutation and its affected pathways in megakaryocytes and platelets: Van Oorschot R et al, Haematologica, January 2019
  2. Inherited missense variants that affect GFI1B function do not necessarily cause bleeding diatheses: Van Oorschot R et al, Haematologica, December 2018

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