EXPRESSION SIGNATURE TO PREDICT MAJOR CYTOGENETIC RESPONSE IN CHRONIC PHASE CML PATIENTS TREATED WITH IMATINIB

Newly diagnosed chronic phase chronic myeloid leukemia (CML) patients with a major cytogenetic response (MCyR) after 12 months of imatinib therapy have an excellent long-term outcome, while patients without MCyR have a high progression risk. Since patients with primary cytogenetic resistance may benefit from more intensive therapy up-front, we sought to identify biomarkers to predict MCyR. Keywords: Two group comparison to identify trasncriptomic signature that predicts response to therapy CD34+ cells were isolated from cryopreserved mononuclear cells of chronic phase CML patients with a complete cytogenetic response (CCyR) or >65% Ph-positive metaphases after 12 months of imatinib therapy (training set N=36). Gene expression profiles generated on amplified RNA using Affymetrix HG-U133 Plus 2.0 arrays were compared between responders and non-responders, using the criteria ANOVA p<0.1 and fold difference >I1.5I. A minimal response classifier derived from the comparison was used to predict response in a prospectively collected validation set using same criteria for responders/nonresponders (N=23).