Acquired genomic copy number changes in CML patients with the Philadelphia chromosome (Ph+)

Chronic myeloid leukemia (CML) is characterized by the BCR-ABL1 fusion gene; this fusion gene is usually a consequence of the Philadelphia (Ph(+)) chromosome, which results from the t(9;22)(q34;q11.2). Patients newly diagnosed with CML are routinely treated with tyrosine kinase inhibitors; however, the clinical course of the disease can vary, and this variance may be associated with genetic heterogeneity. Array comparative genomic hybridization (CGH) technology is a powerful tool for identifying subtle genomic segmental alterations, which can result from either losses or gains of chromosomal material. These changes may reveal the presence of genes that play important roles in disease initiation or progression or in treatment outcomes. To investigate whether subtle somatic copy number changes (CNCs) are commonly present in CML patients, a pilot study of 19 patients with the Ph(+) chromosome, but who were negative for common secondary chromosomal anomalies [+der(22), +8, i(17q), and +19], was conducted using a high-density whole genomic oligonucleotide array CGH analysis. Four of the 19 cases had somatic segmental CNCs, including the loss of 9q34, 15q25.3, and 15q13 and a gain of 7p21.1-p15.3. The findings demonstrate that subtle genomic changes are relatively common in CML patients with a Ph(+) chromosome and that the clinical significance of these findings, especially the newly discovered regions, must be determined in large patient population studies.