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Aberrations identified by genomic arrays in normal karyotype CMML can be detected in 40% of patients, but do not add prognostic information to molecular mutations

Leukemia volume 30, pages 2235–2238 (2016)Cite this article

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Chronic myelomonocytic leukemia (CMML) is a chronic clonal disease characterized by myelodysplastic (MDS) and myeloproliferative (MPN) features.1 It is defined by the occurrence of peripheral blood (PB) monocytosis (>1 × 109/l) without BCR-ABL1 fusion oncogene or PDGFRA or PDGFRB rearrangements. Cases are further subclassified in CMML-1 (<10% blasts in the bone marrow (BM)) and CMML-2 (10–19% blasts), accounting for 80 and 20% of cases, respectively. The genetic landscape is highly heterogeneous. Most frequently mutated genes are TET2 (59–60% of cases), SRSF2 (50–51%), ASXL1 (40–45%), RAS (30%), CBL (15–21%) and SETBP1 (6–15%), whereas TP53 mutations are rare (1%).2, 3 Majority of patients (up to 70%) show normal karyotype (NK), whereas clonal cytogenetic abnormalities have been identified in almost 30% of cases.4 Most frequent abnormalities are trisomy 8 (23%), loss of the Y chromosome (20%), monosomy 7 or 7q deletion (14%), complex karyotype (10%), trisomy 21 (8%), abnormalities of chromosome 3 (8%) and 20q deletion (8%). On the basis of the cytogenetic findings, the Spanish group defined three risk classes, that is, low (–Y and NK), intermediate (karyotype not classified as low or high risk) and high risk (+8 or monosomy 7).4 Balanced rearrangements have been described rarely.5

However, chromosome banding analysis (CBA) shows some limits related to the necessity of in vitro replication of the abnormal clone.6 Moreover, spatial resolution is limited to 10 MB size. Therefore, submicroscopic cytogenetic aberrations cannot be detected. Genomic arrays do not rely on proliferating cells and provide a very high spatial resolution, up to few Kb. Furthermore, arrays can detect not only copy number abnormalities (CNAs), that is, losses and gains, but also copy neutral loss of heterozygosity (CN-LOH).7 However, at least 15% of cells should harbor the genomic abnormality to allow a reliable detection. On the basis of these premises, we aimed to evaluate genomic abnormalities in CMML patients with normal CBA through the application of genomic array.

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Acknowledgements

We would like to thank all physicians for sending samples to MLL laboratory and for providing clinical information. In addition, we would like to thank all the coworkers at the MLL for the great work in performing technical evaluation.

Author contributions

CV performed statistical analysis and wrote the manuscript; CH was responsible for cytogenetics and genomic array; TH was responsible for cytomorphologic analysis; MZ performed cytogenetics and genomic array; NN provided bioinformatic support; WK contributed to statistical analyses; MM investigated molecular mutations 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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Authors and Affiliations

  1. MLL, Munich Leukemia Laboratory, Munich, Germany

    C Vetro, C Haferlach, T Haferlach, M Zenger, N Nadarajah, W Kern & M Meggendorfer

  2. Division of Hematology, Department of Medical and Surgical Specialities, University of Catania, Catania, Italy

    C Vetro

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  1. C Vetro
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Correspondence to M Meggendorfer.

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Competing interests

CH, WK, and TH declare equity ownership of MLL Munich Leukemia Laboratory. NN, MZ and MM are employed by MLL Munich Leukemia Laboratory. CV declares no conflict of interest.

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Vetro, C., Haferlach, C., Haferlach, T. et al. Aberrations identified by genomic arrays in normal karyotype CMML can be detected in 40% of patients, but do not add prognostic information to molecular mutations. Leukemia 30, 2235–2238 (2016). https://doi.org/10.1038/leu.2016.158

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