Translocation t(17;18)(q10;q10)

Abstract

Received July 20, 2000; accepted December 29, 2000. Major recent advances in the treatment of chronic myelogenous leukemia (CML), in particular increased understanding of the role of the Bcr-Abl protein in its pathogenesis and the development of specific tyrosine kinase inhibitors, are leading to effective and nontoxic therapy of this disease. However, the management of advanced disease remains unsatisfactory. The identification of molecular and cytogenetic events leading to disease progression is of interest because treatment can be tailored, based on the likelihood of disease progression related to such events, and, once these events have been identified, it may be possible to identify new targets for the treatment of more advanced stages of the disease. Clonal evolution, the appearance of new chromosomal aberrations in addition to the Philadelphia chromosome (Ph), is an indicator of disease acceleration in CML, occurring in 50 – 80% of patients at the time of progression. The changes reported most frequently are trisomy 8, double Ph, trisomy 19, and abnormalities of chromosome 17, including 17pand isochromosome 17. Other less frequent abnormalities include monosomies of chromosomes 7, 17, and Y, and trisomies of chromosomes 17 and 21. Although recurring chromosomal translocations are being described increasingly in hematologic malignancies, they have not been frequently associated with CML acceleration, with translocation t(3;21) seen only in occasional patients. The importance of identifying new translocations is related to their utility in identifying new genes that are important in leukemogenesis. Several translocations have been characterized in human leukemias. The exact cause of human chromosomal translocations remains unclear. It is not known whether such events are nonspecific, occurring at “fragile” sites within the genome and resulting in a selective growth advantage as a result of their proximity to protooncogenes, or whether such events are more specific, related to topoisomerase II enzyme activity. Several potential mechanisms responsible for nonrandom translocations have been proposed including homologous recombination mediated by Alu elements, translin activity, purine/pyrimidine repeat regions, illegitimate V(D)J recombinations, and topoisomerase II inhibitor effects. –13 Translocation of the long arms between chromosomes 17 and 18, t(17;18), has been reported infrequently in association with hematologic malignancies (Table 1). Of the previously reported 10 cases, only 1 was a patient with CML; the other 9 patients had acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). This led to the suggestion by Jonveaux et al. that this translocation is a nonrandom 1704