Vav1 is a crucial molecule in monocytic/macrophagic differentiation of myeloid leukemia-derived cells

• Published in: Cell and tissue research Vol. 345; no. 1; pp. 163 - 175
• Main Authors: Bertagnolo, Valeria, Nika, Ervin, Brugnoli, Federica, Bonora, Massimo, Grassilli, Silvia, Pinton, Paolo, Capitani, Silvano
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2011; Springer; Springer Nature B.V
• Subjects: Actins - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Adhesion - drug effects; Cell culture; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Nucleus Shape - drug effects; Cell Shape - drug effects; Cellular biology; Cytoskeleton; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Gene Silencing - drug effects; Human Genetics; Humans; Leukemia; Leukemia, Promyelocytic, Acute - metabolism; Leukemia, Promyelocytic, Acute - pathology; Macrophages - drug effects; Macrophages - metabolism; Macrophages - pathology; Molecular biology; Molecular Medicine; Monocytes - drug effects; Monocytes - metabolism; Monocytes - pathology; Muscle proteins; Myelocytic leukemia; Nonlymphoid leukemia; Phenotype; Phosphorylation - drug effects; Phosphotyrosine - metabolism; Proteomics; Proto-Oncogene Proteins c-vav - metabolism; Regular Article; Signal transduction; Tetradecanoylphorbol Acetate - pharmacology; Up-Regulation - drug effects; Monocytic differentiation; Cell culture; Cytoskeleton; Myeloid leukemia; Actin; Vav1
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-011-1195-5

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.