IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease
- Author(s)
- Wong, S; McLaughlin, J; Cheng, DH; Shannon, K; Robb, L; Witte, ON;
- Details
- Publication Year 2003-09-30,Volume 100,Issue #20,Page 11630-11635
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- BCR-ABL expression led to a dramatic up-regulation of the IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor receptor betabeta common (IL-3Rbetac) and IL-3 receptor beta (IL-3Rbeta) 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-3Rbetac/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-3Rbetac chain or both IL-3Rbetac/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-3Rbetac/beta chain could act as a cofactor in BCR-ABL-induced leukemogenesis by activation of its many known oncogenic signaling pathways.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- CHRONIC MYELOID-LEUKEMIA; COLONY-STIMULATING FACTOR; CHRONIC MYELOGENOUS LEUKEMIA; STEM-CELL DIFFERENTIATION; COMMON BETA-SUBUNIT; TYROSINE KINASE; BONE-MARROW; HEMATOPOIETIC PROGENITORS; GROWTH-FACTOR; PHILADELPHIA-CHROMOSOME
- Publisher's Version
- https://doi.org/10.1073/pnas.2035020100
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2003-09-30 12:00:00