REGULAR ARTICLE Vav1 is a crucial molecule in monocytic/macrophagic differentiation of myeloid leukemia-derived cells Valeria Bertagnolo & Ervin Nika & Federica Brugnoli & Massimo Bonora & Silvia Grassilli & Paolo Pinton & Silvano Capitani Received: 13 December 2010 /Accepted: 13 May 2011 /Published online: 7 June 2011 # Springer-Verlag 2011 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 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. Keywords Myeloid leukemia . Vav1 . Monocytic differentiation . Cytoskeleton . Actin . Cell culture Abbreviations ATRA All trans-retinoic acid APL Acute promyelocytic leukemia BSA Bovine serum albumin DAPI 4,6-Diamino-2-phenylindole DABCO 1,4-Diazabicyclo [2.2.2] octane DMSO Dimethyl sulfoxide FBS Fetal bovine serum FITC Fluorescein isothiocyanate GEF Guanine Nucleotide exchange factor PBS Phosphate-buffered saline PIC Piceatannol PMA Phorbol-12-myristate-13-acetate This research was supported by grants from MIUR Cofin (2007) to S. C., MAE (Italy-Croatia bilateral project 2009–2010) to V .B., and local funds from the University of Ferrara (Italy) to S.C. and V .B. V . Bertagnolo (*) : E. Nika : F. Brugnoli : S. Grassilli : S. Capitani Signal Transduction Unit, Section of Human Anatomy, Department of Morphology and Embryology, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy e-mail: bgv@unife.it M. Bonora : P. Pinton Section of General Pathology, Department of Experimental and Diagnostic Medicine, University of Ferrara, 44100 Ferrara, Italy M. Bonora : P. Pinton : S. Capitani Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, 44100 Ferrara, Italy M. Bonora : P. Pinton Emilia Romagna Laboratory, BioPharmaNet, University of Ferrara, 44100 Ferrara, Italy V . Bertagnolo : F. Brugnoli : P. Pinton : S. Capitani Laboratory for advanced technologies and therapies (LTTA), Emilia Romagna Technopole, University of Ferrara, 44100 Ferrara, Italy Cell Tissue Res (2011) 345:163–175 DOI 10.1007/s00441-011-1195-5