Extracellular glycine is necessary for optimal hemoglobinization of erythroid cells
EHA Learning Center. Garcia-Santos D. Aug 1, 2017; 193099
Topic: Section 1: Clinical hematology Benign
Daniel Garcia-Santos
Daniel Garcia-Santos
Login now to access Regular content available to all registered users.

Access to EHA Members only content is an EHA membership benefit.
Click here to join EHA or renew your membership here.


Journal Abstract
Discussion Forum (0)
Rate & Comment (0)

Co-Authors: Ruth M. Scheicher, Karoline Kollmann, Martin Glösmann, Michaela Prchal-Murphy, Anca S. Tigan, Daniela A. Fux, Sandro Altamura, Joana Neves, Martina U. Muckenthaler, Keiryn L. Bennett, Stefan Kubicek, Philip W. Hinds, Marieke von Lindern, Veronika Sexl

Abstract: Mice lacking Cdk6 kinase activity suffer from mild anemia accompanied by elevated numbers of Ter119+ cells in the bone marrow. The animals show hardly any alterations in erythroid development, indicating that Cdk6 is not required for proliferation and maturation of erythroid cells. There is also no difference in stress erythropoiesis following hemolysis in vivo. However, Cdk6−/− erythrocytes have a shortened lifespan and are more sensitive to mechanical stress in vitro, suggesting differences in cytoskeletal architecture. Erythroblasts contain both Cdk4 and Cdk6, while mature erythrocytes apparently lack Cdk4 and their Cdk6 is partly associated with the cytoskeleton. We used mass spectrometry to show that Cdk6 interacts with a number of proteins involved in cytoskeleton organization. Cdk6−/− erythroblasts show impaired F-actin formation and lower levels of gelsolin, which interacts with Cdk6. We also found that Cdk6 regulates the transcription of a panel of genes involved in actin (de-)polymerization. Cdk6-deficient cells are sensitive to drugs that interfere with the cytoskeleton, suggesting that our findings are relevant to the treatment of patients with anemia – and may be relevant to cancer patients treated with the new generation of CDK6 inhibitors.

Article Number: 995

Doi: 10.3324/haematol.2016.159947

Code of conduct/disclaimer available in General Terms & Conditions