title: Genomic, immunophenotypic, and NPM1/FLT3 mutational studies on 17 patients with normal karyotype acute myeloid leukemia (AML) followed by aberrant karyotype AML at relapse.
abstract: Normal karyotype (NK) is the most common cytogenetic group in acute myeloid leukemia (AML) diagnosis; however, up to 50% of these patients at relapse will have aberrant karyotype (AK) AML. To determine the etiology of relapsed AK AML cells, we evaluated cytogenetic, immunophenotypic, and molecular results of 17 patients with diagnostic NK AML and relapsed AK AML at our institute. AK AML karyotype was diverse, involving no favorable and largely (8 of 17) complex cytogenetics. Despite clear cytogenetic differences, immunophenotype and NPM1/FLT3 gene mutation status did not change between presentation and relapse in 83% (10 of 12) and 94% (15 of 16) cases, respectively. High-resolution array-based comparative genomic hybridization (aCGH) performed via paired aCGH on NK AML and AK AML samples from the same patient confirmed cytogenetic aberrations only in the relapse sample. Analysis of 16 additional diagnostic NK AML samples revealed no evidence of submicroscopic aberrations undetected by conventional cytogenetics in any case. These results favor evolution of NK AML leukemia cells with acquisition of novel genetic changes as the most common etiology of AK AML relapse as opposed to secondary leukemogenesis. Additional studies are needed to confirm whether AK AML cells represent selection of rare preexisting clones below aCGH detection and to further characterize the molecular lesions found at time of AK AML relapse.
authors.affiliation: Leukemia Service, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Eunice.wang@roswellpark.org
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
authors.forename: Sheila N J
authors.initials: SN
authors.lastname: Sait
authors.forename: David
authors.initials: D
authors.lastname: Gold
authors.forename: Terry
authors.initials: T
authors.lastname: Mashtare
authors.forename: Petr
authors.initials: P
authors.lastname: Starostik
authors.forename: Laurie Ann
authors.initials: LA
authors.lastname: Ford
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Norma J
authors.initials: NJ
authors.lastname: Nowak
authors.forename: George
authors.initials: G
authors.lastname: Deeb
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D023281:Genomics; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3