p210(BCR-ABL) reprograms transformed and normal human megakaryocytic progenitor cells into erythroid cells and suppresses FLI-1 transcription. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Leukemia Année : 2007

p210(BCR-ABL) reprograms transformed and normal human megakaryocytic progenitor cells into erythroid cells and suppresses FLI-1 transcription.

D. Buet
  • Fonction : Auteur
H. Raslova
  • Fonction : Auteur
P. Jarrier
  • Fonction : Auteur
V. Lazar
  • Fonction : Auteur
A. Turhan
  • Fonction : Auteur
F. Louache
  • Fonction : Auteur

Résumé

The BCR-ABL oncoprotein exhibits deregulated protein tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph)-positive human leukemias. Here, we report that ectopic expression of p210(BCR-ABL) in the megakaryoblastic Mo7e cell line and in primary human CD34(+) progenitors trigger erythroid differentiation at the expense of megakaryocyte (MK) differentiation. Clonal culture of purified CD41(+)CD42(-) cells, a population highly enriched in MK progenitors, combined with the conditional expression of p210(BCR-ABL) tyrosine kinase activity by imatinib identified a true lineage reprogramming. In both Mo7e or CD41(+)CD42(-) cells transduced with p210(BCR-ABL), lineage switching was associated with a downregulation of the friend leukemia Integration 1 (FLI-1) transcription factor. Re-expression of FLI-1 in p210(BCR-ABL)-transduced Mo7e cells rescued the megakaryoblastic phenotype. Altogether, these results demonstrate that alteration of signal transduction via p210(BCR-ABL) reprograms MK cells into erythroid cells by a downregulation of FLI-1. In addition, our findings underscore the role of kinases in lineage choice and infidelity in pathology and suggest that downregulation of FLI-1 may have important implications in CML pathogenesis.

Domaines

Génétique
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Dates et versions

hal-00176495 , version 1 (03-10-2007)

Identifiants

Citer

D. Buet, H. Raslova, J.-F. Geay, P. Jarrier, V. Lazar, et al.. p210(BCR-ABL) reprograms transformed and normal human megakaryocytic progenitor cells into erythroid cells and suppresses FLI-1 transcription.. Leukemia, 2007, 21 (5), pp.917-25. ⟨10.1038/sj.leu.2404600⟩. ⟨hal-00176495⟩
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