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Oligonucleotide array-CGH reveals cryptic gene copy number alterations in karyotypically normal acute myeloid leukemia

Leukemia volume 21, pages 571–574 (2007)Cite this article

In basic cytogenetic analysis 40–50% of acute myeloid leukemia (AML) patients show a normal karyotype. Karyotypically normal AML is a clinically and molecularly heterogeneous group with gene expression changes and frequently mutated genes, such as NPM1 and FLT3 (reviewed by Mrozek et al).1 Because cytogenetic alterations in the leukemic cells are important prognostic factors determining the treatment outcome and survival of AML patients, cryptic copy number alterations could explain some of the heterogeneity. Studies using fluorescence in situ hybridization (FISH) or comparative genomic hybridization (CGH) have either not detected cryptic alterations in karyotypically normal AML or have shown them only in a few cases.2, 3 However, these methods have limitations in resolution or genome coverage. Array-CGH (aCGH) allows genome-wide high-resolution analysis of copy number alterations that are not detectable by standard methods. Recent aCGH analyses have shown new submicroscopic copy number changes in AML with known chromosomal alterations4, 5, 6 but aCGH studies of normal karyotypic cases have not been reported.

To detect submicroscopic copy number alterations in diagnostic samples from 26 AML patients with a normal karyotype, we used oligonucleotide CGH microarrays (44A and 44B) (Agilent Technologies, Santa Clara, CA, USA) that carry 44 000 60-mer genomic probes. The patients had been diagnosed and treated in Helsinki University Central Hospital, Finland. The clinical data are described in Table 1 and Supplementary text.

Table 1 Clinical data, FLT3 and NPM1 mutations, and aCGH results
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Figure 1

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Acknowledgements

This work was supported by grants from the Foundation for the Finnish Cancer Institute and Helsinki University Central Hospital research funds.

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Authors and Affiliations

  1. Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

    A Tyybäkinoja, K Piippo & S Knuutila

  2. Department of Medicine, Division of Hematology, Helsinki University Central Hospital, Helsinki, Finland

    E Elonen

  3. Hematology Research Unit, Biomedicum Helsinki, Helsinki, Finland

    K Porkka

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  1. A Tyybäkinoja
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  2. E Elonen
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Correspondence to S Knuutila.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Tyybäkinoja, A., Elonen, E., Piippo, K. et al. Oligonucleotide array-CGH reveals cryptic gene copy number alterations in karyotypically normal acute myeloid leukemia. Leukemia 21, 571–574 (2007). https://doi.org/10.1038/sj.leu.2404543

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