title: Immunophenotype of acute myeloid leukemia with NPM mutations: prognostic impact of the leukemic compartment size.
abstract: NPM mutations are the most common genetic abnormalities found in non-promyelocytic AML. NPM-positive patients usually show a normal karyotype, a peculiar morphologic appearance with frequent monocytic traits and good prognosis in the absence of an associated FLT3 mutation. This report describes the immunophenotypic and genetic characteristics of a consecutive series of NPM-mutated de novo AML patients enroled in the CETLAM trial. Eighty-three patients were included in the study. Complete immunophenotype was obtained using multiparametric flow cytometry. Associated genetic lesions (FLT3, MLL, CEBPA and WT1 mutations) were studied by standardized methods. Real-time PCR was employed to assess the minimal residual status. The most common pattern was CD34-CD15+ and HLA-DR+. Small CD34 populations with immunophenotypic aberrations (CD15 and CD19 coexpression, abnormal SSC) were detected even in CD34 negative samples. Nearly all cases expressed CD33 (strong positivity), CD13 and CD117, and all were CD123+. The stem cell marker CD110 was also positive in most cases. Biologic parameters such as a high percentage of intermediate CD45+ (blast gate) (>75% nucleated cells), CD123+ and FLT3-ITD mutations were associated with a poor outcome. Quantitative PCR positivity had no prognostic impact either after induction or at the end of chemotherapy. Only PCR positivity (greater than 10 copies) detected in patients in haematological remission was associated with an increased relapse rate. Further studies are required to determine whether the degree of leukemic stem cell expansion (CD45+CD123+cells) increases the risk of acquisition of FLT3-ITD and/or provides selective advantages.
authors.affiliation: Department of Hematology and Laboratory, Hospital de la Santa Creu I Sant Pau, Avda Sant Antoni M Claret 167, 08025 Barcelona, Spain. jnomdedeu@santpau.cat
authors.forename: J
authors.initials: J
authors.lastname: Nomdedeu
authors.forename: E
authors.initials: E
authors.lastname: Bussaglia
authors.forename: N
authors.initials: N
authors.lastname: Villamor
authors.forename: C
authors.initials: C
authors.lastname: Martinez
authors.forename: J
authors.initials: J
authors.lastname: Esteve
authors.forename: M
authors.initials: M
authors.lastname: Tormo
authors.forename: C
authors.initials: C
authors.lastname: Estivill
authors.forename: M P
authors.initials: MP
authors.lastname: Queipo
authors.forename: R
authors.initials: R
authors.lastname: Guardia
authors.forename: M
authors.initials: M
authors.lastname: Carricondo
authors.forename: M
authors.initials: M
authors.lastname: Hoyos
authors.forename: A
authors.initials: A
authors.lastname: Llorente
authors.forename: J
authors.initials: J
authors.lastname: Juncà
authors.forename: M
authors.initials: M
authors.lastname: Gallart
authors.forename: A
authors.initials: A
authors.lastname: Domingo
authors.forename: J
authors.initials: J
authors.lastname: Bargay
authors.forename: M
authors.initials: M
authors.lastname: Mascaró
authors.forename: J M
authors.initials: JM
authors.lastname: Moraleda
authors.forename: L
authors.initials: L
authors.lastname: Florensa
authors.forename: J M
authors.initials: JM
authors.lastname: Ribera
authors.forename: D
authors.initials: D
authors.lastname: Gallardo
authors.forename: S
authors.initials: S
authors.lastname: Brunet
authors.forename: A
authors.initials: A
authors.lastname: Aventin
authors.forename: J
authors.initials: J
authors.lastname: Sierra
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D016162:Genes, Wilms Tumor; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D015703:Antigens, CD; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3