Showing papers by "Derek L. Stirewalt published in 2003"
TL;DR: Exploring the mechanism by which mutations in the FLT3 gene cause uncontrolled proliferation might lead to a better understanding of how cells become cancerous and provide insights for the development of new drugs.
Abstract: Normal haematopoietic cells use complex systems to control proliferation, differentiation and cell death. The control of proliferation is, in part, accomplished through the ligand-induced stimulation of receptor tyrosine kinases, which signal to downstream effectors through the RAS pathway. Recently, mutations in the FMS-like tyrosine kinase 3 (FLT3) gene, which encodes a receptor tyrosine kinase, have been found to be the most common genetic lesion in acute myeloid leukaemia (AML), occurring in approximately 25% of cases. Exploring the mechanism by which these FLT3 mutations cause uncontrolled proliferation might lead to a better understanding of how cells become cancerous and provide insights for the development of new drugs.
850 citations
TL;DR: Activating mutations in the RTK/ras signaling pathway are common in pediatric AML, and their presence may identify a population at higher risk of poor outcome who may benefit from allogeneic BM transplantation.
145 citations
TL;DR: Together, these factors can be used to improve the risk stratification of patients with Ph+ ALL who undergo transplantation, which will greatly enhance the ability to counsel these patients and potentially lead to the development of more specific treatment plans for them.
104 citations
TL;DR: Mevastatin reduces Ras membrane localization, but statin sensitivity in primary AML cells is not consistently associated with ras mutations nor with Ras overexpression, suggesting that another mevalonate pathway by-product(s) is the statin target in at least some AMLs.
63 citations
TL;DR: Some of the signaling pathways that are aberrantly regulated in AML are examined, focusing on the tyrosine kinase/RAS/MAP kinase and JAK/STAT pathways.
43 citations
3 citations
Patent•
04 Nov 2003
TL;DR: In this article, a template-switching oligonucleotide as a template for linearly amplifying cDNA from an RNA molecule was proposed. But it was not shown how to synthesize multiple copies of sense cDNA molecules as templates.
Abstract: In one aspect, the present invention provides methods for linearly amplifying cDNA from an RNA molecule. The methods comprise the steps of: (a) synthesizing an antisense cDNA molecule using an RNA molecule as a template; (b) synthesizing an extended antisense cDNA molecule using a template-switching oligonucleotide as a template; (c) synthesizing multiple copies of sense cDNA molecules using the extended antisense cDNA strand as a template; and (d) generating double-stranded cDNA molecules using the multiple copies of sense cDNA molecules as templates. Another aspect of the invention provides methods for linearly amplifying RNA, comprising the steps o£ (a) using an RNA molecule as a template for synthesizing an antisense cDNA molecule; (b) using a template-switching oligonucleotide as a template for synthesizing an extended antisense cDNA molecule; (c) using the extended antisense cDNA molecule as a template for synthesizing multiple copies of sense cDNA molecules; (d) using the sense cDNA molecules as templates for generating double-stranded cDNA molecules; and (e) using the double-stranded cDNA molecules as templates for synthesizing RNA molecules.
2 citations