Dok1 and dok2 proteins regulate cell cycle in hematopoietic stem and progenitor cells

Emilie Coppin, Maria De Grandis, Pier Paolo Pandolfi, Marie Laure Arcangeli, Michel Aurrand-Lions, Jacques A. Nunès

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

13 Citations (Scopus)

Résumé

Dok1 and Dok2 proteins play a crucial role in myeloid cell proliferation as demonstrated by Dok1 and Dok2 gene inactivation, which induces a myeloproliferative disease in aging mice. In this study, we show that Dok1/Dok2 deficiency affects myeloproliferation even at a young age. An increase in the cellularity of multipotent progenitors is observed in young Dok1/Dok2-deficient mice. This is associated with an increase in the cells undergoing cell cycle, which is restricted to myeloid committed progenitors. Furthermore, cellular stress triggered by 5-fluorouracil (5-FU) treatment potentiates the effects of the loss of Dok proteins on multipotent progenitor cell cycle. In addition, Dok1/Dok2 deficiency induces resistance to 5-FU-induced hematopoietic stem cell exhaustion. Taken together, these results demonstrate that Dok1 and Dok2 proteins are involved in the control of hematopoietic stem cell cycle regulation.

langue originaleAnglais
Pages (de - à)4110-4121
Nombre de pages12
journalJournal of Immunology
Volume196
Numéro de publication10
Les DOIs
étatPublié - 15 mai 2016
Modification externeOui

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