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Lack of noncanonical RAS mutations in cytogenetically normal acute myeloid leukemia

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Abstract

Transforming mutations in RAS genes are commonly found in human malignancies, including myeloid leukemias. To investigate the incidence, spectrum, and distribution of activating K- and N-RAS mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients, 204 CN-AML patients were screened. Activating K- and N-RAS mutations were detected in 3 of 204 (1.5 %) and 22 of 204 (10.8 %) CN-AML samples, respectively. RAS mutated patients presented with a lower percentage of bone marrow blasts (65 vs 80 %, P = 0.022). RAS mutations tended to occur with nucleophosmin-1 (NPM1) mutations (P = 0.079), and all three samples containing K-RAS mutations had concomitant NPM1 mutations. There was no significant overlap between K-RAS mutations and N-RAS, FLT3, CEBPA, IDH1/2, WT1 or MLL mutations. RAS mutation status did not impact relapse-free or overall survival of CN-AML patients. In contrast to reports of noncanonical RAS mutations in other cancers, including some leukemia subtypes, we only observed K- and N-RAS mutations in codons 12, 13, or 61 in CN-AML samples. Our findings suggest that while K-RAS mutations are infrequent in CN-AML, activating K-RAS mutations may cooperate with mutated NPM1 to induce leukemia.

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Acknowledgments

The authors thank E. Lux and K. Görlich for excellent technical support. This work was supported by grants to C.R. from the German José Carreras Leukemia Stiftung (DJCLS R 05/21 and DJCLS R 07/32f).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    Christoph W. M. Reuter, Jürgen Krauter, Fredrick O. Onono, Tania Bunke, Felicitas Thol, Katharina Wagner, Michael Heuser & Arnold Ganser

  2. Klinikum Braunschweig, Braunschweig, Germany

    Jürgen Krauter

  3. Department of Hematology, Oncology, and Tumor Immunology, Charité, Berlin, Germany

    Frederik Damm

  4. Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany

    Gudrun Göhring & Brigitte Schlegelberger

  5. Institute of Experimental Hematology, Hannover Medical School (MHH), Carl-Neuberg Str. 1, 30625, Hannover, Germany

    Michael A. Morgan

Authors
  1. Christoph W. M. Reuter
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  2. Jürgen Krauter
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  3. Fredrick O. Onono
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  4. Tania Bunke
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  7. Katharina Wagner
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  8. Gudrun Göhring
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  9. Brigitte Schlegelberger
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  10. Michael Heuser
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  11. Arnold Ganser
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Corresponding author

Correspondence to Michael A. Morgan.

Additional information

Christoph W. M. Reuter and Jürgen Krauter contributed equally to this work.

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Reuter, C.W.M., Krauter, J., Onono, F.O. et al. Lack of noncanonical RAS mutations in cytogenetically normal acute myeloid leukemia. Ann Hematol 93, 977–982 (2014). https://doi.org/10.1007/s00277-014-2061-9

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  • DOI: https://doi.org/10.1007/s00277-014-2061-9

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