To develop the AML induction response test for elderly AML patients, Nodality scientists first profiled two separate training sets of AML samples to identify nodes (signaling molecules perturbed by therapies or other factors) that correlated with a clinical response to standard induction therapy. Nodes tested included growth factor responsive nodes, cytokine responsive nodes, surface markers (e.g. cKIT, Flt3 Receptor) and apoptosis-related nodes. Several nodes predicted response to induction therapy and were superior to standard diagnostic criteria such as age and cytogenetic testing results.
Next, a separate and independent study was performed to confirm the nodes found in the prior studies as well as to build a final test model to predict response. Again, the model remained predictive when analyzed alongside traditional factors such as age, cytogenetic status and performance status. The final test is currently being validated in elderly adults with AML and is designed to be run as a laboratory service in Nodality's CLIA-certified reference laboratory. The test has also been developed according to FDA Design Control and related principles.
AML: Surface Receptors & Intracellular Pathways Investigated
More information can be found in the following publications and presentations:
Signaling changes in the stem cell factor–AKT-S6 pathway in diagnostic AML samples.
Kornblau SM, Covey T, Putta S, Cohen A, Woronicz J, Fantl WJ, Gayko U, and Cesano A.
Blood Cancer Journal. (2011) 1, e3; doi:10.1038/bcj.2010.2.
Functional characterization of FLT3 receptor signaling deregulation in acute myeloid leukemia by single cell network profiling (SCNP).
Rosen DB, Minden MD, Kornblau SM, Cohen A, Gayko U, Putta S, Woronicz J, Evensen E, Fantl WJ, and Cesano A.
Plos One. 2010;5(10):e13543.
Modulated multiparametric phosphoflow cytometry in hematological malignancies: technology and clinical applications.
Covey TM and Cesano A.
Best Pract Res Clin Haematol. 2010;23(3):319-31.
Distinct patterns of DNA damage response and apoptosis correlate with Jak/Stat and PI3Kinase response profiles in human acute myelogenous leukemia.
Rosen DB, Putta S, Covey T, Huang Y-W, Nolan GP, Cesano A, Minden MD, and Fantl WJ.
Plos One. 2010;5(8):e12405.
Dynamic single cell network profiles in AML are associated with patient response to standard induction therapy.
Kornblau SM, Minden MD, Rosen DB, Putta S, Cohen A, Covey T, Spellmeyer DC, Fantl WJ, Gayko U, and Cesano A.
Clin Cancer Res. 2010;16:3721-33.
Insights into acute myeloid leukemia via single cell network profiling.
Kornblau A, Minden SM, Hogge D, Cohen A, and Cesano A.
CLi. 2010;34:12-5.