Isodicentric Philadelphia Chromosome: A Rare Chromosomal Aberration in Imatinib-Resistant Chronic Myelogenous Leukemia Patients - Case Report with Review of the Literature.

The BCR-ABL1 fusion gene derived from the Philadelphia chromosome, resulting from a classical translocation event t(9;22)(q34.13;q11.23), is responsible for the pathogenesis of chronic myeloid leukemia (CML) in more than 90% of the patients. The isoderivative chromosome 22, ider(22), and relative amplification or duplication of the BCR-ABL1 gene have been considered as one of the major reasons associated with the resistance to chemotherapy with imatinib mesylate, but the data remain unclear. GTG-banding together with FISH were performed to identify the presence of the ider(22) chromosome. Reverse transcription-polymerase chain reaction (RT-PCR) for the detection of BCR-ABL1 fusion transcripts and BCR-ABL1 kinase domain mutation analysis were carried out in this study. Conventional and molecular cytogenetic analysis on metaphase chromosomes confirmed the presence of ider(22) chromosomes in both patients. Molecular characterization revealed the presence of a 210-kDa BCR-ABL1 type b3a2 and lack of mutations at the kinase domain region on the fusion product in both patients. The occurrence of the ider(22) chromosome could be considered as an important marker correlated with the aggressive progression of CML as well as the emergence of drug-resistant cell clones.