文章基本信息

标题：IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease
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作者：Stephane Wong ; Jami McLaughlin ; Donghui Cheng 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：20
页码：11630-11635
DOI：10.1073/pnas.2035020100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：BCR-ABL expression led to a dramatic up-regulation of the IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor receptor {beta} common (IL-3R{beta}c) and IL-3 receptor {beta} (IL-3R{beta}) 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-3R{beta}c/{beta} 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-3R{beta}c chain or both IL-3R{beta}c/{beta} 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-3R{beta}c/{beta} chain could act as a cofactor in BCR-ABL-induced leukemogenesis by activation of its many known oncogenic signaling pathways.