In chronic myeloid leukemia white cells from cytogenetic responders and non-responders to imatinib have very similar gene expression signatures

Oregon Health & Science University Cancer Institute, Portland, OR 97239, USA. L.C.Crossman@ncl.ac.uk

BACKGROUND AND OBJECTIVES: Imatinib induces complete cytogenetic responses (CCR) in the majority of patients with chronic myeloid leukemia (CML) in chronic phase (CP). However, a subgroup of patients is refractory at the cytogenetic level. Clinically, it would be advantageous to identify such patients a priori, since they may benefit from more aggressive therapy. DESIGN AND METHODS: To elucidate mechanisms underlying cytogenetic refractoriness, we used Affymetrix oligonucleotide arrays to determine the transcriptional signature associated with cytogenetic refractoriness in unselected white blood or bone marrow cells from 29 patients with CML in first CP prior to treatment with imatinib. Patients with CCR within 9 months were defined as responders (n = 16) and patients lacking a major cytogenetic response (> 35% Philadelphia-positive metaphases) after 1 year were defined as non-responders (n = 13). RESULTS: Differences in gene expression between responders and non-responders were subtle. Stringent statistical analysis with multiple comparison adjustments revealed very few differentially expressed genes. Differentially expressed genes could not be confirmed in an independent test set. INTERPRETATION AND CONCLUSIONS: We conclude that transcriptional profiling of unselected white cells is of limited value for identifying genes consistently associated with cytogenetic refractoriness to imatinib.

This article has been cited by other articles:

				M. Baccarani, G. Saglio, J. Goldman, A. Hochhaus, B. Simonsson, F. Appelbaum, J. Apperley, F. Cervantes, J. Cortes, M. Deininger, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet Blood, September 15, 2006; 108(6): 1809 - 1820. [Abstract] [Full Text] [PDF]

				H. Li and M. Zhan Systematic intervention of transcription for identifying network response to disease and cellular phenotypes Bioinformatics, January 1, 2006; 22(1): 96 - 102. [Abstract] [Full Text] [PDF]

				T. Hughes ABL Kinase Inhibitor Therapy for CML: Baseline Assessments and Response Monitoring Hematology, January 1, 2006; 2006(1): 211 - 218. [Abstract] [Full Text] [PDF]

				A. S. M. Yong, R. M. Szydlo, J. M. Goldman, J. F. Apperley, and J. V. Melo Molecular profiling of CD34+ cells identifies low expression of CD7, along with high expression of proteinase 3 or elastase, as predictors of longer survival in patients with CML Blood, January 1, 2006; 107(1): 205 - 212. [Abstract] [Full Text] [PDF]

				M. W.N. Deininger Management of Early Stage Disease Hematology, January 1, 2005; 2005(1): 174 - 182. [Abstract] [Full Text] [PDF]