Chronic myeloid leukaemia (CML) is a clonal stem cell disorder, characterized at the cytogenetic level by the presence of a balanced chromosomal rearrangement, the t (9; 22) or Philadelphia chromosome (Ph) translocation and at the molecular level by the presence of the BCR-ABL fusion gene. 1 Several lines of evidence point to deregulated expression of the BCR-ABL tyrosine kinase as the initial genomic lesion in CML. 1 Despite the presence of a consistent genetic abnormality, however, CML patients display considerable clinical heterogeneity, the basis of which is poorly understood. This heterogeneity was well characterized by Sokal et al. 2 and is reflected 24 years later by the varying responses to treatment in chronic phase patients treated with a tyrosine kinase inhibitor. 3 We therefore used a novel ultra-high-resolution genomic screening assay to search for additional acquired genomic abnormalities that might explain this clinical heterogeneity and help to assess prognosis for individual patients. DNA was extracted from the polymorphonuclear cells in bone marrow samples from 10 previously untreated chronic phase patients. These patients subsequently received imatinib and achieved complete cytogenetic responses, at which point further polymorphonuclear-derived DNA was prepared. Comparative genomic hybridization (CGH) was performed with a 2.1 million oligonucleotide array (NimbleGen, Milton Keynes, UK;‘HD2’070713_HG18_WG_CGH_HX1 design). The probes on this array were selected to achieve a uniform distribution throughout the genome, with approximately one probe every 1200bp. Each DNA sample from diagnosis was competitively hybridized against the same patient’s remission sample, which avoided detection of constitutional polymorphic copy number variants and limited results to acquired leukemiarelated changes. Scanned array images were imported into NimbleScan (NimbleGen) to identify copy number aberrations (CNAs) from HD2 image and intensity data. Nexus 3 software (BioDiscovery Inc., El Segundo, CA, USA) was used to visualize the normalized segmented data. For representative CNAs the CGH result was confirmed by fluorescence in situ hybridization or quantitative real-time PCR.

All 10 CML patient samples harboured detectable genomic imbalances with an average of 53 CNAs per patient (range: 4–166). Of the 530 CNAs detected 381 (72%) were amplifications and 149 (28%) were deletions. Two hundred and fifty two CNAs (48%) involved at least one known gene. Many of the CNAs that involved single genes contained the complete gene with only small quantities of adjacent non-coding DNA. The average size