title: Hyperdiploidy associated with T315I mutation in BCR-ABL kinase domain in an accelerated phase-chronic myeloid leukemia case.
abstract: BACKGROUND
  Chronic myeloid leukemia (CML) is genetically characterized by the occurrence of a reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22, i.e. the Philadelphia (Ph) chromosome. During CML progression 60-80% of the cases acquire additional genetic changes. Even though hyperdiploidy is not a rare finding in advanced phase-CML, hyperdiploidy together with a T315I kinase domain (KD) mutation in the BCR-ABL gene has not yet been reported.
  
  
  RESULTS
  A complete cytogenetic and molecular cytogenetic analysis; molecular biology methods such as quantitative reverse transcription polymerase chain reaction (RQ-PCR) and allele-specific oligonucleotide (ASO)-PCR; and immunophenotypically confirmed CML in acceleration phase (AP). Our case revealed the presence of hyperdiploidy including multiple copies of the Ph chromosome, presence of b3a2 fusion transcript,T315I mutation in BCR-ABL KD in pre imatinib mesylate (IM) treatment. The ratio of BCR-ABL/ABL expression in post nilotinib treatment was 0.07% on international scale.
  
  
  CONCLUSIONS
  The patient demonstrated a good response to nilotinib after imatinib failure; while the hyperdiploid clone disappeared the T315I mutation remained during follow-up. The underlying mechanisms and prognostic implications of these cytogenetic abnormalities are discussed.
authors.affiliation: Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission, P.O. Box 6091 Damascus, Syria.
authors.forename: Walid
authors.initials: W
authors.lastname: Al-Achkar
authors.affiliation: Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission, P.O. Box 6091 Damascus, Syria.
authors.forename: Faten
authors.initials: F
authors.lastname: Moassass
authors.affiliation: Mammalians Biology Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission, Damascus, Syria.
authors.forename: Adnan
authors.initials: A
authors.lastname: Ikhtiar
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena, Germany.
authors.forename: Moneeb Abdullah Kassem
authors.initials: MA
authors.lastname: Othman
authors.affiliation: Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission, P.O. Box 6091 Damascus, Syria.
authors.forename: Abdulsamad
authors.initials: A
authors.lastname: Wafa
keywords: Chronic myeloid leukemia; Hyperdiploidy; Philadelphia chromosome; Prognostic factors; T315I mutation