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Al-Achkar W, Moassass F, Ikhtiar A, et al. Hyperdiploidy associated with T315I mutation in BCR-ABL kinase domain in an accelerated phase-chronic myeloid leukemia case. Mol Cytogenet. 2014;7(1):89doi: 10.1186/s13039-014-0089-0.
Al-Achkar, W., Moassass, F., Ikhtiar, A., Liehr, T., Othman, M. A., & Wafa, A. (2014). Hyperdiploidy associated with T315I mutation in BCR-ABL kinase domain in an accelerated phase-chronic myeloid leukemia case. Molecular cytogenetics, 7(1), 89. https://doi.org/10.1186/s13039-014-0089-0
Al-Achkar, Walid, et al. "Hyperdiploidy associated with T315I mutation in BCR-ABL kinase domain in an accelerated phase-chronic myeloid leukemia case." Molecular cytogenetics vol. 7,1 (2014): 89. doi: https://doi.org/10.1186/s13039-014-0089-0
Al-Achkar W, Moassass F, Ikhtiar A, Liehr T, Othman MA, Wafa A. Hyperdiploidy associated with T315I mutation in BCR-ABL kinase domain in an accelerated phase-chronic myeloid leukemia case. Mol Cytogenet. 2014 Nov 29;7(1):89. doi: 10.1186/s13039-014-0089-0. eCollection 2014. PMID: 25621010; PMCID: PMC4305221.
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Mol Cytogenet. 2014 Nov 29;7(1):89. doi: 10.1186/s13039-014-0089-0. eCollection 2014.

Hyperdiploidy associated with T315I mutation in BCR-ABL kinase domain in an accelerated phase-chronic myeloid leukemia case.

Molecular cytogenetics

Walid Al-Achkar, Faten Moassass, Adnan Ikhtiar, Thomas Liehr, Moneeb Abdullah Kassem Othman, Abdulsamad Wafa

Affiliations

  1. Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission, P.O. Box 6091 Damascus, Syria.
  2. Mammalians Biology Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission, Damascus, Syria.
  3. Institute of Human Genetics, Jena University Hospital, Jena, Germany.

PMID: 25621010 PMCID: PMC4305221 DOI: 10.1186/s13039-014-0089-0

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.

Keywords: Chronic myeloid leukemia; Hyperdiploidy; Philadelphia chromosome; Prognostic factors; T315I mutation

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