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Chronic myelogenous leukemia

Cytogenetic landscape and impact in blast phase of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy

Leukemia volume 31, pages 585–592 (2017)Cite this article

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Abstract

The landscape of additional chromosomal alterations (ACAs) and their impact in chronic myeloid leukemia, blast phase (CML-BP) treated with tyrosine kinase inhibitors (TKIs) have not been well studied. Here, we investigated a cohort of 354 CML-BP patients treated with TKIs. We identified +8, an extra Philadelphia chromosome (Ph), 3q26.2 rearrangement, −7 and isochromosome 17q (i(17q)) as the major-route changes with a frequency of over 10%. In addition, +21 and +19 had a frequency of over 5%. These ACAs demonstrated lineage specificity: +8, 3q26.2 rearrangement, i(17q) and +19 were significantly more common in myeloid BP, and −7 more common in lymphoid BP; +Ph and +21 were equally distributed between two groups. Pearson correlation analysis revealed clustering of common ACAs into two groups: 3q26.2 rearrangement, −7 and i(17q) formed one group, and other ACAs formed another group. The grouping correlated with risk stratification of ACAs in CML, chronic phase. Despite the overall negative prognostic impact of ACAs, stratification of ACAs into major vs minor-route changes provided no prognostic relevance in CML-BP. The emergence of 3q26.2 rearrangement as a major-route change in the TKI era correlated with a high frequency of ABL1 mutations, supporting a role for TKI resistance in the changing cytogenetic landscape in CML-BP.

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Authors and Affiliations

  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Z Chen, W Wang, Z Zuo, L J Medeiros & S Hu

  2. Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China

    Z Chen

  3. Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    C Shao

  4. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    X Mou

  5. Department of Mechanical Engineering, The University of Michigan, Ann Arbor, MI, USA

    S J Hu

  6. Department of Pathology, Hartford Hospital, Hartford, CT, USA

    J A DiGiuseppe

  7. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA

    Y Zu

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Chen, Z., Shao, C., Wang, W. et al. Cytogenetic landscape and impact in blast phase of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Leukemia 31, 585–592 (2017). https://doi.org/10.1038/leu.2016.231

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