Novel biomarkers for individualized therapy in acute myeloid leukemia

Jenny Forshed, Petra Hååg, Lena Kanter, Janne Lehtiö, Johan Lengqvist, Rolf Lewensohn, Marita Lindberg, Jacob Odeberg, Lukas Orre, Maria Pernemalm, Birgitta Sundelin and Kristina Viktorsson.

Yudi Pawitan, MEB, KI

This is a translational research project applying proteomics in the treatment of acute myeloid leukemia (AML). Our aim is to discover proteomic determinants related to drug response and clinical outcome in AML, using both cell line model systems and clinical material. The discovered key proteins will undergo validation using molecular biology methods as well as a larger patient material cohort to asses the potential of these proteins as biomarkers for individualized therapy. Furthermore, the proteomic profiling and cellular signalling studies will be linked as spin-off projects to a large multi-centre phase III clinical trial, where gemtuzumab ozogamicin (GO, Mylotarg™) is administered to newly diagnosed adult AML patients. The PI of this KBC project is also the PI for this clinical study in Sweden. GO is a novel drug consisting of a monoclonal antibody against the CD33 antigen conjucated to a toxin, gamma calicheamicin. The cellular response of leukemic cells to the DNA-damaging calicheamicin will be studied in detail to reveal associated proteome expressions. This AML-proteomics project will constitute an integrated effort involving experts in clinical hematology, hematopathology, protein chemistry, high resolution and high through-put proteomics and mass spectrometry, biostatistics and bioinformatics, as well as molecular biology. The project is aimed at promoting further development of the truly translational cancer proteomics platform at Karolinska Clinical Biomics Center (KBC).

Last updated: 2008-01-14