title: Activating mutations in NOTCH1 in acute myeloid leukemia and lineage switch leukemias.
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.
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.
authors.forename: T
authors.initials: T
authors.lastname: Palomero
authors.forename: K
authors.initials: K
authors.lastname: McKenna
authors.forename: J
authors.initials: J
authors.lastname: O-Neil
authors.forename: I
authors.initials: I
authors.lastname: Galinsky
authors.forename: R
authors.initials: R
authors.lastname: Stone
authors.forename: K
authors.initials: K
authors.lastname: Suzukawa
authors.forename: E
authors.initials: E
authors.lastname: Stiakaki
authors.forename: M
authors.initials: M
authors.lastname: Kalmanti
authors.forename: E A
authors.initials: EA
authors.lastname: Fox
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: J C
authors.initials: JC
authors.lastname: Aster
authors.forename: A T
authors.initials: AT
authors.lastname: Look
authors.forename: A A
authors.initials: AA
authors.lastname: Ferrando
mesh_terms: D000208:Acute Disease; D001483:Base Sequence; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics*; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology*; D017354:Point Mutation; D051881:Receptor, Notch1 / Q000235:genetics*; D012008:Recurrence; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1