Annals of Hematology

, Volume 93, Issue 6, pp 977–982

Lack of noncanonical RAS mutations in cytogenetically normal acute myeloid leukemia

  • Christoph W. M. Reuter
  • Jürgen Krauter
  • Fredrick O. Onono
  • Tania Bunke
  • Frederik Damm
  • Felicitas Thol
  • Katharina Wagner
  • Gudrun Göhring
  • Brigitte Schlegelberger
  • Michael Heuser
  • Arnold Ganser
  • Michael A. Morgan
Original Article

DOI: 10.1007/s00277-014-2061-9

Cite this article as:
Reuter, C.W.M., Krauter, J., Onono, F.O. et al. Ann Hematol (2014) 93: 977. doi:10.1007/s00277-014-2061-9
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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.

Keywords

RASMutationNPM1Cytogenetically normal AML

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Christoph W. M. Reuter
    • 1
  • Jürgen Krauter
    • 1
    • 2
  • Fredrick O. Onono
    • 1
  • Tania Bunke
    • 1
  • Frederik Damm
    • 3
  • Felicitas Thol
    • 1
  • Katharina Wagner
    • 1
  • Gudrun Göhring
    • 4
  • Brigitte Schlegelberger
    • 4
  • Michael Heuser
    • 1
  • Arnold Ganser
    • 1
  • Michael A. Morgan
    • 5
  1. 1.Department of Hematology, Hemostasis, Oncology and Stem Cell TransplantationHannover Medical SchoolHannoverGermany
  2. 2.Klinikum BraunschweigBraunschweigGermany
  3. 3.Department of Hematology, Oncology, and Tumor ImmunologyCharitéBerlinGermany
  4. 4.Institute of Cell and Molecular PathologyHannover Medical SchoolHannoverGermany
  5. 5.Institute of Experimental HematologyHannover Medical School (MHH)HannoverGermany