Vav promotes differentiation of human tumoral myeloid precursors

Valeria Bertagnolo, Federica Brugnoli, Carlo Mischiati, Alessia Sereni, Alberto Bavelloni, Cinzia Carini, Silvano Capitani

Research output: Contribution to journalArticle

Abstract

Vav is one of the genetic markers that correlate with the differentiation of hematopoietic cells. In T and B cells, it appears crucial for both development and functions, while, in non-lymphoid hematopoietic cells, Vav seems not involved in cell maturation, but rather in the response of mature cells to agonist-dependent proliferation and phagocytosis. We have previously demonstrated that the amount and the tyrosine phosphorylation of Vav are up-regulated in both whole cells and nuclei of tumoral promyelocytes induced to granulocytic maturation by ATRA and that tyrosine-phosphorylated Vav does not display any ATRA-induced GEF activity but contributes to the regulation of PI 3-K activity. In this study, we report that Vav accumulates in nuclei of ATRA-treated APL-derived cells and that the down-modulation of Vav prevents differentiation of tumoral promyelocytes, indicating that it is a key molecule in ATRA-dependent myeloid maturation. On the other hand, the overexpression of Vav induces an increased expression of surface markers of granulocytic differentiation without affecting the maturation-related changes of the nuclear morphology. Consistent with an effect of Vav on the transcriptional machinery, array profiling shows that the inhibition of the Syk-dependent tyrosine phosphorylation of Vav reduces the number of ATRA-induced genes. Our data support the unprecedented notion that Vav plays crucial functions in the maturation process of myeloid cells, and suggest that Vav can be regarded as a potential target for the therapeutic treatment of myeloproliferative disorders.

Original languageEnglish
Pages (from-to)56-63
Number of pages8
JournalExperimental Cell Research
Volume306
Issue number1
DOIs
Publication statusPublished - May 15 2005

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Keywords

  • Acute promyelocytic leukemia (APL)
  • All-trans retinoic acid (ATRA)
  • Granulocytic differentiation
  • Tyrosine phosphorylation
  • Vav

ASJC Scopus subject areas

  • Cell Biology

Cite this

Bertagnolo, V., Brugnoli, F., Mischiati, C., Sereni, A., Bavelloni, A., Carini, C., & Capitani, S. (2005). Vav promotes differentiation of human tumoral myeloid precursors. Experimental Cell Research, 306(1), 56-63. https://doi.org/10.1016/j.yexcr.2004.12.001