Italian Journal of Anatomy and Embryology - contenuto non piu disponibile

Vav1 is a critical signal transducer for both the development and function of normal hematopoietic cells, in which it regulates the acquisition of maturation-related properties, including adhesion, motility, and phagocytosis. Vav1 is also important for the agonist-induced maturation of acute promyelocytic leukemia (APL)-derived promyelo- cytes, in which it promotes the acquisition of a mature phenotype by playing multiple functions at both cytoplas- mic and nuclear levels. We investigated the possible role of Vav1 in the differentiation of leukemic precursors to mono- cytes/macrophages. Tumoral promyelocytes in which Vav1 was negatively modulated were induced to differentiate into monocytes/macrophages with phorbol-12-myristate-13-ace- tate (PMA) and monitored for their maturation-related properties. We found that Vav1 was crucial for the phenotyp- ical differentiation of tumoral myeloid precursors to mono- cytes/macrophages, in terms of CD11b expression, adhesion capability and cell morphology. Confocal analysis revealed that Vav1 may synergize with actin in modulating nuclear morphology of PMA-treated adherent cells. Our data indicate that, in tumoral promyelocytes, Vav1 is a compo- nent of lineage-specific transduction machineries that can be recruited by various differentiating agents. Since Vav1 plays a central role in the completion of the differentiation program of leukemic promyelocytes along diverse hemato- poietic lineages, it can be considered a common target for developing new therapeutic strategies for the various subtypes of myeloid leukemias.