title: Rapid screening of ASXL1, IDH1, IDH2, and c-CBL mutations in de novo acute myeloid leukemia by high-resolution melting.
abstract: Recently, many novel molecular abnormalities were found to be distinctly associated with acute myeloid leukemia (AML). However, their clinical relevance and prognostic implications are not well established. We developed a new combination of high-resolution melting assays on a LightCycler 480 and direct sequencing to detect somatic mutations of ASXL1 (exon 12), IDH1 (exon 4), IDH2 (exon 4), and c-CBL (exons 8 and 9) genes to know their incidence and prognostic effect in a cohort of 175 patients with de novo AML: 16 patients (9%) carried ASXL1 mutations, 16 patients had IDH variations (3% with IDH1(R132) and 6% with IDH2(R140)), and none had c-CBL mutations. Patients with ASXL1 mutations did not harbor IDH1, [corrected] or CEBPA mutations, and a combination of ASXL1 and IDH2 mutations was found only in one patient. In addition, we did not find IDH1 and FLT3 or CEBPA mutations concurrently or IDH2 with CEBPA. IDH1 and IDH2 mutations were mutually exclusive. Alternatively, NPM1 mutations were concurrently found with ASXL1, IDH1, or IDH2 with a variable incidence. Mutations were not significantly correlated with any of the clinical and biological features studied. High-resolution melting is a reliable, rapid, and efficient screening technique for mutation detection in AML. The incidence for the studied genes was in the range of those previously reported. We were unable to find an effect on the outcome.
authors.affiliation: Department of Hematology, University Hospital La Fe, Valencia, Spain. ibanyez_marcom@gva.es
authors.forename: Mariam
authors.initials: M
authors.lastname: Ibáñez
authors.forename: Esperanza
authors.initials: E
authors.lastname: Such
authors.forename: José
authors.initials: J
authors.lastname: Cervera
authors.forename: Irene
authors.initials: I
authors.lastname: Luna
authors.forename: Inés
authors.initials: I
authors.lastname: Gómez-Seguí
authors.forename: María
authors.initials: M
authors.lastname: López-Pavía
authors.forename: Sandra
authors.initials: S
authors.lastname: Dolz
authors.forename: Eva
authors.initials: E
authors.lastname: Barragán
authors.forename: Oscar
authors.initials: O
authors.lastname: Fuster
authors.forename: Marta
authors.initials: M
authors.lastname: Llop
authors.forename: Rebeca
authors.initials: R
authors.lastname: Rodríguez-Veiga
authors.forename: Amparo
authors.initials: A
authors.lastname: Avaria
authors.forename: Silvestre
authors.initials: S
authors.lastname: Oltra
authors.forename: M Leonor
authors.initials: ML
authors.lastname: Senent
authors.forename: Federico
authors.initials: F
authors.lastname: Moscardó
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.forename: David
authors.initials: D
authors.lastname: Martínez-Cuadrón
authors.forename: Guillermo
authors.initials: G
authors.lastname: Martín
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005820:Genetic Testing / Q000191:economics / Q000379:methods*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D013997:Time Factors; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; C000716967:NPM1 protein, human; D012097:Repressor Proteins; D000090243:Nucleophosmin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D050721:Proto-Oncogene Proteins c-cbl