Effect of TP53 contact and conformational mutations on cell survival and erythropoiesis of human hematopoietic stem cells in a long term culture model
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Azam Salari1, Kathrin Thomay1, Jana Lentes1, Juliane Ebersold1, Maike Hagedorn1, Britta Skawran1, Claudia Davenport1, Axel Schambach2, Brigitte Schlegelberger1 and Gudrun Göhring1
1Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany
2Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany
Gudrun Göhring, email: Goehring.Gudrun@MH-Hannover.de
Keywords: TP53 mutation; hematopoietic stem cells (HSCs); haematopoiesis; erythropoiesis; MDS
Received: July 15, 2017 Accepted: May 19, 2018 Published: July 06, 2018
TP53 deficiencies characterize myeloid malignancies with a dismal prognosis. To unravel the pathomechanism of TP53 mutations in the development of myeloid malignancies, we analyzed the functional properties of TP53 conformational and contact mutations and TP53 loss in human CD34+ cells. We show for the first time that the analyzed conformational mutations lead to higher cell viability in human hematopoietic stem progenitor cells. In contrast to these conformational mutations, contact mutations interfered with efficient erythropoiesis.
These findings show that not only the detection of a TP53 mutation is important, but also the specific mutation may play a role in malignant transformation and progression.
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