IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease
AUTOR(ES)
Wong, Stephane
FONTE
National Academy of Sciences
RESUMO
BCR-ABL expression led to a dramatic up-regulation of the IL-3, IL-5, and granulocyte–macrophage colony-stimulating factor receptor β common (IL-3Rβc) and IL-3 receptor β (IL-3Rβ) chains in murine embryonic stem cell-derived hematopoietic cells coincident with an expansion of multipotent progenitors and myeloid elements. This up-regulation required BCR-ABL tyrosine kinase activity and led to IL-3Rβc/β chain tyrosine phosphorylation in the absence of detectable IL-3 production. These results suggested that cytokine-independent IL-3 receptor activation could be a dominant signaling component in BCR-ABL-induced leukemogenesis. To unambiguously define the significance of IL-3 receptor-dependent signaling in BCR-ABL-induced leukemogenesis, BCR-ABL-transduced bone marrow cells deficient in either IL-3Rβc chain or both IL-3Rβc/β chain expression were examined for their ability in generating myeloproliferative disease (MPD). These BCR-ABL-expressing knockout cells were capable of generating MPD similar to control cells, demonstrating that IL-3 receptor activation is not essential for BCR-ABL-induced MPD. However, the IL-3Rβc/β chain could act as a cofactor in BCR-ABL-induced leukemogenesis by activation of its many known oncogenic signaling pathways.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=208809Documentos Relacionados
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