Similar Molecular Alterations Occur in Related Leukemias With and Without the Philadelphia Chromosome

Abstract

The reciprocal translocation between the long arms of chromosomes 9 and 22, t(9:22), results in the Philadelphia (Ph1) chromosome, the karyotypic hallmark of chronic myeloid leukaemia (CML) [1]. The molecular consequences of this translocation have been well characterized, although their contribution to the disease process is less clear. The translocation creates a hybrid transcription unit consisting of the 5′ end of the so-called breakpoint cluster region (bcr) gene on ch22q11 and the c-abl proto-oncogene on ch9q34 [2]. This new gene is capable of being expressed as a chimeric 8.7 kb mRNA [3] which, when translated, produces a fusion protein (p210) with an enhanced phosphorylating activity [4] compared, in vitro, to the normal c-abl protein (p145).