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The landscape of myeloid neoplasms with isochromosome 17q discloses a specific mutation profile and is characterized by an accumulation of prognostically adverse molecular markers

Leukemia volume 30, pages 1624–1627 (2016)Cite this article

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Isochromosome 17 (i(17)(q10)) is a rare cytogenetic abnormality resulting in the loss of the short arm and duplication of the long arm of chromosome 17.1 I(17)(q10) has been reported in different myeloid neoplasms, like acute myeloid leukemia (AML), chronic myeloid leukemia (CML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap, as well as in Hodgkin lymphoma and other lymphomas.2 I(17)(q10) has been described both as primary and as secondary chromosomal aberration. The overall frequency is low with 1–2% in entities other than CML.3 However, in accelerated phase or blast crises of CML i(17)(q10) has been identified as frequently occurring secondary aberration, indicating a poor prognosis. Usually i(17)(q10) occurs in a complex karyotype, but is also found as sole abnormality as well as with one additional aberration. It is believed that i(17)(q10) as a sole abnormality in myeloid neoplasms defines a distinctive clinicopathological entity with high risk of leukemic progression and poor prognosis,4, 5 although it is specifically mentioned only briefly in the WHO classification.6 The description of myeloid neoplasms that carry a i(17)(q10) and have <20% blasts remains difficult. Patients show mixed features of myeloproliferation and dysplasia, associated with pseudo-Pelger-Huet anomaly of the neutrophils.2, 4 Most cases show a prominent monocytic component and therefore might meet criteria for chronic myelomonocytic leukemia (CMML). However, often the designation to MDS/MPN, unclassifiable with isolated i(17)(q10) is most appropriate.6 Therefore, we aimed at comprehensively characterizing the molecular features of patients with myeloid neoplasms and i(17)(q10).

To address this issue we selected patients by the presence of i(17)(q10) and diagnosis of a myeloid neoplasm (n=62), but excluded patients with BCR-ABL1/Philadelphia positive CML. The selected cohort comprised of 47 males and 15 females with a median age of 69 years (range: 30–87 years). Classification of all cases was performed by cytomorphology on peripheral blood and/or bone marrow smears according to the WHO classification.6 All samples were analyzed by next generation sequencing using a 29-gene panel targeting ASXL1, BCOR, BRAF, CALR, CBL, CSF3R, DNMT3A, ETV6, EZH2, FLT3-TKD, GATA1, GATA2, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, PTPN11, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53, U2AF1 and WT1. Variants of unknown significance were excluded from statistical analyses (n=14). Chromosome banding and fluorescence in situ hybridization analysis were performed in all cases, a subset of cases with sole i(17)(q10) were additionally analyzed by array CGH (19/27). For further patient characteristics as well as methodical details see Supplementary Information.

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Acknowledgements

We thank all clinicians for sending samples to our laboratory for diagnostic purposes and for providing clinical information and follow-up data. In addition, we would like to thank all the co-workers at the MLL Munich Leukemia Laboratory for approaching together many aspects in the field of leukemia diagnostics and research.

Author contributions

MM investigated molecular mutations, analyzed the data and wrote the manuscript; CH was responsible for cytogenetics; WK was involved in statistical analyses; MZ performed array CGH; KM characterized morphological findings; TH was responsible for cytomorphologic analysis and was involved in the collection of clinical data as well as manuscript preparation. All authors read and contributed to the final version of the manuscript.

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  1. MLL Munich Leukemia Laboratory, Munich, Germany

    M Meggendorfer, C Haferlach, M Zenger, K Macijewski, W Kern & T Haferlach

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  1. M Meggendorfer
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Correspondence to M Meggendorfer.

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CH, WK and TH declare equity ownership of MLL Munich Leukemia Laboratory. MM, MZ and KM are employed by MLL Munich Leukemia Laboratory.

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Supplementary Information accompanies this paper on the Leukemia website

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Meggendorfer, M., Haferlach, C., Zenger, M. et al. The landscape of myeloid neoplasms with isochromosome 17q discloses a specific mutation profile and is characterized by an accumulation of prognostically adverse molecular markers. Leukemia 30, 1624–1627 (2016). https://doi.org/10.1038/leu.2016.21

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