title: Vav1 is a crucial molecule in monocytic/macrophagic differentiation of myeloid leukemia-derived cells.
abstract: 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 promyelocytes, in which it promotes the acquisition of a mature phenotype by playing multiple functions at both cytoplasmic and nuclear levels. We investigated the possible role of Vav1 in the differentiation of leukemic precursors to monocytes/macrophages. Tumoral promyelocytes in which Vav1 was negatively modulated were induced to differentiate into monocytes/macrophages with phorbol-12-myristate-13-acetate (PMA) and monitored for their maturation-related properties. We found that Vav1 was crucial for the phenotypical differentiation of tumoral myeloid precursors to monocytes/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 component 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 hematopoietic lineages, it can be considered a common target for developing new therapeutic strategies for the various subtypes of myeloid leukemias.
authors.affiliation: Signal Transduction Unit, Section of Human Anatomy, Department of Morphology and Embryology, University of Ferrara, Via Fossato di Mortara 66, Ferrara, Italy. bgv@unife.it
authors.forename: Valeria
authors.initials: V
authors.lastname: Bertagnolo
authors.forename: Ervin
authors.initials: E
authors.lastname: Nika
authors.forename: Federica
authors.initials: F
authors.lastname: Brugnoli
authors.forename: Massimo
authors.initials: M
authors.lastname: Bonora
authors.forename: Silvia
authors.initials: S
authors.lastname: Grassilli
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
authors.forename: Silvano
authors.initials: S
authors.lastname: Capitani
mesh_terms: D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D053144:Cell Nucleus Shape / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000199:Actins; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; D019000:Phosphotyrosine; D013755:Tetradecanoylphorbol Acetate