CST Demonstrates the Discovery Capabilities of PhosphoScan® Proteomics Platform
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Cell Signaling Technology, Inc. has announced the publication of discovery research based on its patent-pending PhosphoScan® proteomics technology, which identified a mutant JAK3 tyrosine kinase as a novel driver in acute myeloid leukemia (AML).
The discovery was published in the July 17, 2006, issue of the journal Cancer Cell, and involved a collaboration between CST and the laboratories of Drs. Brian Druker and Gary Gilliland, at Oregon Health Science University (OHSU) and Brigham & Women's Hospital, respectively.
CST applied its PhosphoScan® platform and proteomics expertise to identify Phospho-Signatures™ - profiles consisting of hundreds of tyrosine phosphorylated proteins - for a panel of AML cell lines where the disease mechanism was unknown.
PhosphoScan® proteomics is an effective strategy for unbiased determination of cellular phospho-profiles, which point directly to kinase drivers of transformation and cancer.
It involves a patent-pending method for immunoaffinity purification of phosphopeptides coupled to mass spectroscopic sequence and phosphorylation site determination.
CST has performed extensive PhosphoScan® analyses of cancer cell lines and primary tumor tissues in which it has discovered many important disease mechanisms involving activated tyrosine kinases, and identified over fifteen thousand phosphorylation sites.
CST has also provided PhosphoScan® analysis for many clients in the pharmaceutical industry for lead kinase inhibitor phospho-profiling with the objective of enabling novel response biomarker assay development.
"The strategy of using PhosphoScan® to quickly reveal the profile of essentially every active and phosphorylated tyrosine kinase in a cell or tissue sample provides a huge breakthrough in our ability to determine cancer mechanisms in cell lines and human tumors," said Dr. Roberto Polakiewicz, CST's Chief Scientific Officer.
"PhosphoScan® proteomics was the key to revealing constitutively active JAK3 in one of the AML cell lines that we profiled and it was within the context of our very productive collaboration with the Druker and Gilliland labs that we were able to discover the activating mutation in JAK3 and its oncogenic activity," said Dr. Brian Druker, JELD-WEN Chair of Leukemia Research at OHSU.
"We have applied the PhosphoScan® profiling strategy to many other cancer cell lines and primary tumor samples and have been equally successful in discovering tyrosine kinase targets that are active and directly involved in transformation."
"These results demonstrate the value of PhosphoScan® in identifying and validating disease targets, and we are confident that PhosphoScan® discoveries will enable improved selection and stratification of patients for kinase targeted therapeutic treatment."
"This approach gives us a way to figure out what's driving the growth of a cancer in an individual patient and ultimately match that patient with the right drug."
"If you try to sift through DNA, it takes almost a year, whereas this technique takes a couple of months and further automation would make it even quicker," Dr. Druker added.
