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Acute Leukemias

Activating mutations in NOTCH1 in acute myeloid leukemia and lineage switch leukemias

Leukemia volume 20, pages 1963–1966 (2006)Cite this article

Abstract

Activating mutations in NOTCH1 are found in over 50% of human T-cell lymphoblastic leukemias (T-ALLs). Here, we report the analysis for activating NOTCH1 mutations in a large number of acute myeloid leukemia (AML) primary samples and cell lines. We found activating mutations in NOTCH1 in a single M0 primary AML sample, in three (ML1, ML2 and CTV-1) out of 23 AML cell lines and in the diagnostic (myeloid) and relapsed (T-lymphoid) clones in a patient with lineage switch leukemia. Importantly, the ML1 and ML2 AML cell lines are derived from an AML relapse in a patient initially diagnosed with T-ALL. Overall, these results demonstrate that activating mutations in NOTCH1 are mostly restricted to T-ALL and are rare in AMLs. The presence of NOTCH1 mutations in myeloid and T-lymphoid clones in lineage switch leukemias establishes the common clonal origin of the diagnostic and relapse blast populations and suggests a stem cell origin of NOTCH1 mutations during the molecular pathogenesis of these tumors.

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Acknowledgements

We thank Kelly Barnes for outstanding technical assistance. This work was supported by the WOLF Trust (AAF), Children's Leukemia Research Association (AAF), Pardee Cancer Research Foundation (AAF), a Pollin research Award (AAF) and NIH Grants CA109901 (ATL) and CA68484 (ATL).

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Authors and Affiliations

  1. Institute for Cancer Genetics, Columbia University, New York, NY, USA

    T Palomero & A A Ferrando

  2. Department of Pathology, Columbia University Medical Center, New York, NY, USA

    T Palomero & A A Ferrando

  3. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Harvard University, Boston, MA, USA

    K McKenna, J O-Neil & A T Look

  4. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School,

    I Galinsky & R Stone

  5. Harvard University, Boston, MA, USA

    I Galinsky & R Stone

  6. Clinical and Experimental Hematology Department, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan

    K Suzukawa

  7. Department of Pediatric Hematology-Oncology, University of Crete, Heraklion Crete, Greece

    E Stiakaki & M Kalmanti

  8. Molecular Diagnostics Laboratory, Microarray Core, Dana-Farber Cancer Institute, Harvard University, Boston, MA, USA

    E A Fox

  9. Internal Medicine-Hematology Oncology Department, Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    M A Caligiuri

  10. Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA

    J C Aster

  11. Department of Pediatrics, Columbia University Medical Center, New York, NY, USA

    A A Ferrando

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  1. T Palomero
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  2. K McKenna
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  3. J O-Neil
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  4. I Galinsky
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  6. K Suzukawa
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  7. E Stiakaki
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  10. M A Caligiuri
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  11. J C Aster
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  12. A T Look
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  13. A A Ferrando
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Corresponding author

Correspondence to A A Ferrando.

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

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Palomero, T., McKenna, K., O-Neil, J. et al. Activating mutations in NOTCH1 in acute myeloid leukemia and lineage switch leukemias. Leukemia 20, 1963–1966 (2006). https://doi.org/10.1038/sj.leu.2404409

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  • DOI: https://doi.org/10.1038/sj.leu.2404409

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