title: Novel mutations of the nucleophosmin (NPM-1) gene in Egyptian patients with acute myeloid leukemia: a pilot study.
abstract: Mutations of the nucleophosmin (NPM-1) gene have been reported in 50-60% of acute myeloid leukemia (AML) patients with normal karyotype. This work was designed to study the prevalence and nature of NPM1 gene mutations in a group of Egyptian patients with AML to get an idea about the profile of NPM1 gene mutations in our society. In 45 previously untreated patients with de novo AML, peripheral blood and/or bone marrow samples from all patients were subjected to microscopic morphologic examination, cytochemical analysis, immunophenotyping and karyotyping. Patients with normal cytogenetic results were selected for molecular analysis of NPM1 exon 12 by PCR amplification followed by DNA sequencing of the amplified product. Twenty-one patients (46.7%) had abnormal karyotype: six cases with t(15;17), five cases with t(8;21), five cases had trisomy 8, two cases carrying inv(3) and three cases had monosomy 7. The remaining 24 patients (53.3%) had normal karyotype. These patients were then subjected to molecular analysis. Out of these 24 patients with normal karyotype, mutant NPM-1 was detected in 11 patients (45.8%) by DNA sequencing; 2 cases showed type A mutation, 2 cases were harboring [ins 1015-1019 (CACG)], with point mutation [1006C>G], while the remaining 7 cases showed heterozygous deletion of nt A [del 1178 (A)].
  
  
  CONCLUSIONS
  Two novel NPM1 gene mutations were detected among our study population of AML patients identified as: the insertion CACG associated with point mutation, deletion of one base, or associated with point mutation. NPM1 gene mutations may become a new tool for monitoring minimal residual disease in AML with normal karyotype. Whether these previously unreported NPM-1 mutations will confer the same better outcome as previously reported mutations is currently unknown and warrants a larger study.
  
  
  CONCLUSIONS
  Two novel NPM1 gene mutations were detected among our study population of AML patients identified as: the insertion CACG associated with point mutation, deletion of one base, or associated with point mutation. NPM1 gene mutations may become a new tool for monitoring minimal residual disease in AML with normal karyotype. Whether these previously unreported NPM-1 mutations will confer the same better outcome as previously reported mutations is currently unknown and warrants a larger study.
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Cairo University, Egypt. nkkassem@hotmail.com
authors.forename: Neemat
authors.initials: N
authors.lastname: Kassem
authors.forename: Alaa Abel
authors.initials: AA
authors.lastname: Hamid
authors.forename: Tarek
authors.initials: T
authors.lastname: Attia
authors.forename: Sherif
authors.initials: S
authors.lastname: Baathallah
authors.forename: Somaya
authors.initials: S
authors.lastname: Mahmoud
authors.forename: Eman
authors.initials: E
authors.lastname: Moemen
authors.forename: Ezzat
authors.initials: E
authors.lastname: Safwat
authors.forename: Mohamed
authors.initials: M
authors.lastname: Khalaf
authors.forename: Olfat
authors.initials: O
authors.lastname: Shaker
mesh_terms: D059786:Abnormal Karyotype; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004534:Egypt; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D054643:INDEL Mutation; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D010865:Pilot Projects; D055815:Young Adult
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin