Study involves detection of small duplications and point mutations in the FLT3 gene, implicated in the pathogenesis of acute myeloid leukemia and is the target of several investigational drugs.
Transgenomic reports that its Wave System will be cited in several presentations at the American Society of Hematology (ASH) annual meeting this month (December 2003) in San Diego, Calif.
Two of these presentations involve the analysis of genes that have been implicated in the pathogenesis of leukemia and identified as targets for therapeutic intervention.
A research team led by Giovanni Martinelli has used Transgenomic's Wave System in two leukemia-related studies.
The first describes detection of mutations in the BCR-ABL gene that are potentially associated with resistance to therapy with the novel tyrosine kinase inhibitor imatinib in chronic myeloid leukemia patients.
The other study involves detection of small duplications and point mutations in the FLT3 gene, which has been implicated in the pathogenesis of acute myeloid leukemia and is the target of several investigational drugs.
The group's work on the FLT3 gene has also resulted in two recent publications in the October issues of Clinical Chemistry and The Lancet Oncology.
Martinelli commented on the significance of this body of work and the role of the Wave System.
"Several FLT3 inhibitors are under investigation for treatment of acute myelogenous leukemia".
"These drug candidates have varying degrees of effectiveness against leukemic cells with different FLT3 abnormalities, making thorough analysis of the FLT3 gene in patient populations critical." Martinelli continued: "The traditional approach of screening for FLT3 alterations involves PCR amplifications and gel electrophoresis".
"This approach is cumbersome, and more importantly, fails to detect very small internal tandem duplications as well as point mutations".
"Our methodology, based on use of the Wave System, has proven capable of detecting all types of alterations in the FLT3 gene, including unanticipated mutations, with sensitivity and specificity approaching 100%." Transgenomic scientists, led by Stan Lilleberg, director of discovery services, recently presented results of Wave-based FLT3 analyses at the Association for Molecular Pathology's annual meeting held Nov 20-23 in Orlando, Fla.
According to Lilleberg, "Our platforms, particularly the Wave HS System, offer the analytical sensitivity required to scan and/or score for mutations that may only be present in a small percentage of leukemic cells".
"Compared to other approaches, we have been able to demonstrate increased analytical sensitivity for detection of both internal tandem duplications and point mutations, by detecting variants present in less than 1% of the total FLT3 gene copies." He concluded, "We believe this has important implications for the development of targeted therapeutics, selection of appropriate therapeutic strategies for individual patients and post-treatment monitoring." Other presentations by Transgenomic's customers at the ASH meeting will cover various topics in a number of different scientific sessions that include prognostic and diagnostic markers in leukemia, minimum residual disease and diagnostic markers, pathogenesis/biology of myeloproliferative disorders and von Willebrand Disease.
