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

Leukemia. 2006 Nov;20(11):1963-6. doi: 10.1038/sj.leu.2404409. Epub 2006 Sep 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Base Sequence
  • Cell Line, Tumor
  • Cell Lineage / genetics*
  • Gene Deletion
  • Gene Expression Regulation, Leukemic*
  • Hematopoietic Stem Cells / pathology
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / pathology*
  • Point Mutation
  • Receptor, Notch1 / genetics*
  • Recurrence
  • T-Lymphocytes / pathology


  • NOTCH1 protein, human
  • Receptor, Notch1