Fiche publication
Date publication
août 2016
Journal
Experimental hematology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BASTIE Jean-Noël
,
Dr DELVA Laurent
,
Dr QUERE Ronan
,
Dr CHRETIEN Marie-Lorraine
,
Dr AUCAGNE Romain
Tous les auteurs :
Chrétien ML, Legouge C, Martin RZ, Hammann A, Trad M, Aucagne R, Largeot A, Bastie JN, Delva L, Quéré R
Lien Pubmed
Résumé
Trim33/Tif1γ (Trim33) is a member of the tripartite motif family. Using a conditional hematopoietic-specific Trim33 knock-out (Trim33(Δ/Δ)) mouse, we showed previously that Trim33 deficiency in hematopoietic stem cells leads to severe defects in hematopoiesis, resembling the main features of human chronic myelomonocytic leukemia. We also demonstrated that Trim33 is involved in hematopoietic aging through TGFβ signaling. Nevertheless, how Trim33 contributes to the terminal stages of myeloid differentiation remains to be clarified. We reveal here the crucial role of Trim33 expression in the control of mature granulomonocytic differentiation. An important component of Trim33-deficient mice is the alteration of myeloid differentiation, as characterized by dysplastic features, abnormal granulocyte and monocyte maturation, and the expansion of CD11b(+)Ly6G(high)Ly6C(low) myeloid cells, which share some features with polymorphonuclear-myeloid-derived suppressor cells. Moreover, in Trim33(Δ/Δ) mice, we observed the alteration of CSF-1-mediated macrophage differentiation in association with the lack of Csf-1 receptor. Altogether, these results indicate that Trim33 deficiency leads to the expansion of a subset of myeloid cells characterizing the myelodysplastic/myeloproliferative neoplasm.
Référence
Exp. Hematol.. 2016 Aug;44(8):727-739.e6
