title: Loss of the NPM1 gene in myeloid disorders with chromosome 5 rearrangements.
abstract: The assignment with chromosome banding techniques of the breakpoints of the recurrent translocation t(3;5) which leads to NPM1/MLF1 gene fusion in myeloid malignancies has not been unequivocal. In order to assess whether this is due to uncertainty in interpretation of the observed banding pattern or whether it reflects true genomic heterogeneity, we decided to analyze the breakpoint positions using fluorescence in situ (FISH) techniques in eight patients with myeloid malignancies and rearrangements of chromosomes 3 and 5. In three patients, colocalization of the NPM1 and MLF1 spanning BACs was demonstrated and NPM1/MLF1 fusion shown by PCR in one while in the remaining cases breakpoints were located outside the NPM1 and MLF1 loci. Interestingly, loss of a copy of the NPM1 gene was found in three of these latter patients. This findings suggest that haploinsufficiency of NPM1 may play a role in subtypes of myelodysplasias and leukemias.
authors.affiliation: 1EMI 0210 Hôpital Necker-Enfants Malades, Paris, France. berger@necker.fr
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: M
authors.initials: M
authors.lastname: Busson
authors.forename: L
authors.initials: L
authors.lastname: Baranger
authors.forename: C
authors.initials: C
authors.lastname: Hélias
authors.forename: M
authors.initials: M
authors.lastname: Lessard
authors.forename: N
authors.initials: N
authors.lastname: Dastugue
authors.forename: F
authors.initials: F
authors.lastname: Speleman
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: C120078:NPM-MLF1 protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000090243:Nucleophosmin