title: Multiple copies of BCR-ABL fusion gene on two isodicentric Philadelphia chromosomes in an imatinib mesylate-resistant chronic myeloid leukemia patient.
abstract: The so-called Philadelphia (Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) cases. Amplification or duplication of the BCR-ABL gene has been found to be one of the key factors leading to drug resistance to imatinib mesylate (IM). In the present study, we identified the presence of isodicentric Ph chromosomes [idic(Ph)] in an IM-resistant patient. Fluorescencein situhybridization (FISH) analysis on metaphase chromosomes confirmed the heterogeneity and amplification of the fused BCR-ABL gene. FISH analysis superimposed on G-banding confirmed the presence of idic(Ph) chromosomes. Reverse transcription-polymerase chain reaction (RT-PCR) products revealed the presence of the BCR-ABL fusion transcript b3a2. The idic(Ph) chromosomes in CML were shown to be fused at the satellite regions of the short arms. The patient did not respond to IM chemotherapy and did not achieve remission. In this study, the impact of the idic(Ph) chromosomes on genomic instability, heterogeneity and amplification of the BCR-ABL gene in IM-resistant patients is discussed.
authors.affiliation: Department of Molecular Biology and Biotechnology, Human Genetics Division, Atomic Energy Commission, Damascus, Syria ;
authors.forename: Walid
authors.initials: W
authors.lastname: Al-Achkar
authors.forename: Abdulsamad
authors.initials: A
authors.lastname: Wafa
authors.forename: Faten
authors.initials: F
authors.lastname: Moassass
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Klein
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
keywords: chronic myeloid leukemia; fluorescence in situ hybridization; imatinib mesylate; isodicentric Philadelphia chromosomes