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Vav1 is a crucial molecule in monocytic/macrophagic differentiation of myeloid leukemia-derived cells.
- Source :
-
Cell & Tissue Research . Jul2011, Vol. 345 Issue 1, p163-175. 13p. - Publication Year :
- 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 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0302766X
- Volume :
- 345
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cell & Tissue Research
- Publication Type :
- Academic Journal
- Accession number :
- 62519404
- Full Text :
- https://doi.org/10.1007/s00441-011-1195-5