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Cancer Cytogenetics pp 33–61Cite as

Chronic Myeloid Leukemia: Cytogenetic Methods and Applications for Diagnosis and Treatment

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 730))

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease caused by recombination between the BCR gene on chromosome 22 and the ABL1 gene on chromosome 9. This rearrangement generates the BCR–ABL1 fusion gene that characterizes leukemic cells in all CML cases. In about 90% of cases, the BCR–ABL1 rearrangement is manifest cytogenetically by the Philadelphia (Ph) chromosome, a derivative of the reciprocal translocation t(9;22)(q34;q11.2). For the remaining cases, recombination may be more complex, involving BCR, ABL1, and genomic sites on one or more other chromosomal regions, or it may occur cryptically within an apparently normal karyotype. Detection of the Ph and associated t(9;22) translocation is a recognized clinical hallmark for CML diagnosis. The disease has a natural multistep pathogenesis, and during chronic phase CML, the t(9;22) or complex variant is usually the sole abnormality. In 60–80% of cases, additional cytogenetic changes appear and often forecast progression to an accelerated disease phase or a terminal blast crisis. Because new frontline therapies such as imatinib specifically target the abnormal protein product of the BCR–ABL1 fusion gene to eliminate BCR–ABL1 positive cells, there is a new reliance on the cytogenetic evaluation of bone marrow cells at diagnosis, then at regular posttreatment intervals. Combined with other parameters, presence or absence of Ph-positive cells in the bone marrow is a powerful early indicator for clinical risk stratification. Cytogenetic changes detected at any stage during treatment, including in the BCR–ABL1-negative cells, may also provide useful prognostic information. Laboratory methods detailed here extend from initial collection of peripheral blood or bone marrow samples through cell culture with or without synchronization, metaphase or interphase harvest, hypotonic treatment and fixation, slide preparation for G-banding or fluorescent in situ hybridization (FISH), and final interpretation.

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Acknowledgments

The author acknowledges generous sponsorship of the Cancer Society of New Zealand that has made this work possible; past and present staff and students of the Cancer Genetics Research Group for their support and inspiration; Margaret McDonald and other members of the Cytogenetic and Molecular Oncology Sections, Canterbury Health Laboratories for devoted technical assistance and contributions to Figs. 1 and 4.

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  1. Cancer Genetics Research Group, Department of Pathology, University of Otago Christchurch School of Medicine and Health Services, Christchurch, New Zealand

    Christine M. Morris

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  1. Victorian Cancer Cytogenetics Service, St. Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, 3065, Victoria, Australia

    Lynda J. Campbell

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Morris, C.M. (2011). Chronic Myeloid Leukemia: Cytogenetic Methods and Applications for Diagnosis and Treatment. In: Campbell, L. (eds) Cancer Cytogenetics. Methods in Molecular Biology, vol 730. Humana Press. https://doi.org/10.1007/978-1-61779-074-4_4

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