1. ¹Institute for Cancer Genetics, Columbia University, New York, NY, USA
2. ²Department of Pathology, Columbia University Medical Center, New York, NY, USA
3. ³Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Harvard University, Boston, MA, USA
4. ⁴Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Harvard University, Boston, MA, USA
5. ⁵Clinical and Experimental Hematology Department, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
6. ⁶Department of Pediatric Hematology-Oncology, University of Crete, Heraklion Crete, Greece
7. ⁷Molecular Diagnostics Laboratory, Microarray Core, Dana-Farber Cancer Institute, Harvard University, Boston, MA, USA
8. ⁸Internal Medicine-Hematology Oncology Department, Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
9. ⁹Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
10. ¹⁰Department of Pediatrics, Columbia University Medical Center, New York, NY, USA

Correspondence: Dr AA Ferrando, Institute for Cancer Genetics, Columbia University, 1130 St Nicholas Avenue, Room 901B, New York, NY 10032, USA. E-mail: af2196@columbia.edu

Received 29 June 2006; Revised 11 August 2006; Accepted 17 August 2006; Published online 28 September 2006.

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.