Effects of retinoic acid, other differentiation inducers and neurotrophic factors on leukemia differentiation
by Ping Xie
THESIS
1997
Ph.D. Biology
xxvii, 251 leaves : ill. (some col.) ; 30 cm
Abstract
Retinoic acid and several other differentiation inducers, including vitamin D3, sodium butyrate and arabinofuranosyl cytosine, have been recognized as promising drugs for differentiation therapy. In light of the recent evidence that retinoic acid induced the expression of the receptors for neurotrophic factors in neuroblastoma and embryonal carcinoma cells, we examined the ability of retinoic acid and several other differentiation inducers to regulate the expression of neurotrophic factors and receptors in leukemia cells. We found that the expression of TrkA and gp130 was induced in several leukemia cell lines by many of the differentiation inducers examined. Moreover, the differentiating effects of these inducers on leukemia cells could be potentiated by the addition of nerve growth fa...[ Read more ]
Retinoic acid and several other differentiation inducers, including vitamin D3, sodium butyrate and arabinofuranosyl cytosine, have been recognized as promising drugs for differentiation therapy. In light of the recent evidence that retinoic acid induced the expression of the receptors for neurotrophic factors in neuroblastoma and embryonal carcinoma cells, we examined the ability of retinoic acid and several other differentiation inducers to regulate the expression of neurotrophic factors and receptors in leukemia cells. We found that the expression of TrkA and gp130 was induced in several leukemia cell lines by many of the differentiation inducers examined. Moreover, the differentiating effects of these inducers on leukemia cells could be potentiated by the addition of nerve growth factor (NGF) or interleukin-6 (IL-6), the cognate ligands for TrkA and gp130, respectively. Therefore, our results demonstrated that TrkA and gp130 are two of the essential genes which are up-regulated by various differentiation inducers and mediate the lineage-specific differentiating effects of these inducers in leukemia cells. Our findings support the intriguing possibility that NGF not only play pivotal roles in the nervous system, but may also exert a broad range of actions in hematopoietic differentiation. Furthermore, the synergistic effects observed in our studies suggested that NGF and IL-6 may have therapeutic potential in the treatment of leukemia, especially when administered in combination with certain differentiation inducer(s).
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