Genomic instability in chronic myeloid leukemia: targets for therapy?

Philadelphia positive (Ph+) chronic myeloid leukemia (CML) is characterized by the occurrence of nonrandom genetic and cytogenetic abnormalities during disease progression. Many of these abnormalities are markers for genes which, when altered, can drive the blastic transformation process. Thus, such genetic alterations may be manifestations of an underlying genomic instability resulting from a compromised DNA damage and repair response, leading to advanced stages of CML and resistance to therapy. This article examines the molecular pathways that may lead to genomic instability in CML and the potential of these pathway constituents to be therapeutic targets.