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Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: Amplification discloses overexpression of APP , ETS2 , and ERG genes

Open access
Baldus, Claudia D., Liyanarachchi, Sandya, Mrózek, Krzysztof, Auer, Herbert, Tanner, Stephan M., Guimond, Martin, Ruppert, Amy S., Mohamed, Nehad, Davuluri, Ramana V., Caligiuri, Michael A., Bloomfield, Clara D., de la Chapelle, Albert·2004·Proceedings of the National Academy of Sciences

Abstract

Molecular mechanisms of leukemogenesis have been successfully unraveled by studying genes involved in simple rearrangements including balanced translocations and inversions. In contrast, little is known about genes altered in complex karyotypic abnormalities. We studied acute myeloid leukemia (AML) patients with complex karyotypes and abnormal chromosome 21. High-resolution bacterial artificial chromosome (BAC) array-based comparative genomic hybridization disclosed amplification predominantly in the 25- to 30-megabase (MB) region that harbors the APP gene (26.3 MB) and at position 38.7-39.1 MB that harbors the transcription factors ERG and ETS2 . Using oligonucleotide arrays, APP was by far the most overexpressed gene (mean fold change 19.74, P = 0.0003) compared to a control group of AML with normal cytogenetics; ERG and ETS2 also ranked among the most highly expressed chromosome 21 genes. Overexpression of APP and ETS2 correlated with genomic amplification, but high APP expression occurred even in a subset of AML patients with normal cytogenetics (10 of 64, 16%). APP encodes a glycoprotein of unknown function previously implicated in Alzheimer's disease, but not in AML. We hypothesize that APP and the transcription factors ERG and ETS2 are altered by yet unknown molecular mechanisms involved in leukemogenesis. Our results highlight the value of molecularly dissecting leukemic cells with complex karyotypes.

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Metadata

Authors
Baldus, C. D., Liyanarachchi, S., Mrózek, K., Auer, H., Tanner, S. M., Guimond, M., Ruppert, A. S., Mohamed, N., Davuluri, R. V., Caligiuri, M. A., Bloomfield, C. D., & de la Chapelle, A.
Venue
Proceedings of the National Academy of Sciences
Published
2004-03-08
Volume
101
Issue
11
Pages
3915-3920
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2137991845
Cited by
173
References
2
FWCI
7.55
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: Amplification discloses overexpression of APP , ETS2 , and ERG genes. https://app.cochat.ai/papers/10.1073/pnas.0400272101
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Baldus, C. D., Liyanarachchi, S., Mrózek, K., Auer, H., Tanner, S. M., Guimond, M., Ruppert, A. S., Mohamed, N., Davuluri, R. V., Caligiuri, M. A., Bloomfield, C. D., & de la Chapelle, A. (2004). Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: Amplification discloses overexpression of APP , ETS2 , and ERG genes. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0400272101

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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