A novel cytogenetic abnormality t(7;8)(p11.2:q11.2) and a four-way Philadelphia translocation in an imatinib mesylate‑resistant chronic myeloid leukemia patient

Al‑Achkar,Walid; Aljapawe,Abdulmunim; Almedani,Suher; Liehr,Thomas; Wafa,Abdulsamad

doi:10.3892/ol.2012.1037

A novel cytogenetic abnormality t(7;8)(p11.2:q11.2) and a four-way Philadelphia translocation in an imatinib mesylate‑resistant chronic myeloid leukemia patient

Authors:
- Walid Al‑Achkar
- Abdulmunim Aljapawe
- Suher Almedani
- Thomas Liehr
- Abdulsamad Wafa
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Affiliations: Department of Molecular Biology and Biotechnology, Human Genetics Division, Atomic Energy Commission, Damascus 6091, Syria, Flow‑Cytometry Laboratory, Department of Molecular Biology and Biotechnology, Mammalians Biology Division, Atomic Energy Commission, Damascus 6091, Syria, Department of Molecular Biology and Biotechnology, Human Genetics Division, Atomic Energy Commission, Damascus 6091, Syria, Jena University Hospital, Institute of Human Genetics, Jena 07743, Germany
Published online on: November 21, 2012 https://doi.org/10.3892/ol.2012.1037
Pages: 617-620

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Abstract

Chronic myelogenous leukemia (CML) is characterized by the Philadelphia (Ph) chromosome, created by a reciprocal translocation t(9:22)(q34;q11) which forms the chimeric gene, BCR‑ABL. Variant Ph chromosome translocations involving chromosomes other than 9 and 22 have been identified in 5‑10% of CML cases. Four‑way Ph chromosome translocations are an extremely rare event in myeloid malignancies and the phenotypic consequences of such rearrangements have not been investigated. Deletions in chromosome 9 are known to be associated with a poor prognosis. In the present study, a novel case of Ph chromosome‑positive CML in blast crisis is reported. A four‑way Ph translocation was identified, involving five chromosomal regions, 9p21, 9q34, 12p13.3, 20q11.2 and 22q11.2, as well as an unbalanced translocation, der(7)t(7;8)(p11.2;q11.2). Since the majority of CML cases are currently treated with imatinib, variant rearrangements in general have no specific prognostic significance, although the mechanisms involved in resistance to therapy have yet to be investigated. In the present case, multiple partial deletions, including ABL and ASS genes on chromosome 9, the region 7p11.2 to 7pter, 8q11.2 to 8pter and two regions on chromosome 12, were identified. An additional Ph chromosome was also detected. Immunophenotyping indicated that the patient had biphenotypic leukemia. The patient did not respond positively to imatinib chemotherapy and died for unknown reasons, one month after diagnosis. The underlying mechanisms and prognostic implications of these cytogenetic abnormalities are discussed.

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