title: SNP array-based karyotyping: differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes.
abstract: In aplastic anemia (AA), contraction of the stem cell pool may result in oligoclonality, while in myelodysplastic syndromes (MDS) a single hematopoietic clone often characterized by chromosomal aberrations expands and outcompetes normal stem cells. We analyzed patients with AA (N = 93) and hypocellular MDS (hMDS, N = 24) using single nucleotide polymorphism arrays (SNP-A) complementing routine cytogenetics. We hypothesized that clinically important cryptic clonal aberrations may exist in some patients with BM failure. Combined metaphase and SNP-A karyotyping improved detection of chromosomal lesions: 19% and 54% of AA and hMDS cases harbored clonal abnormalities including copy-neutral loss of heterozygosity (UPD, 7%). Remarkably, lesions involving the HLA locus suggestive of clonal immune escape were found in 3 of 93 patients with AA. In hMDS, additional clonal lesions were detected in 5 (36%) of 14 patients with normal/noninformative routine cytogenetics. In a subset of AA patients studied at presentation, persistent chromosomal genomic lesions were found in 10 of 33, suggesting that the initial diagnosis may have been hMDS. Similarly, using SNP-A, earlier clonal evolution was found in 4 of 7 AA patients followed serially. In sum, our results indicate that SNP-A identify cryptic clonal genomic aberrations in AA and hMDS leading to improved distinction of these disease entities.
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Manuel G
authors.initials: MG
authors.lastname: Afable
authors.forename: Marcin
authors.initials: M
authors.lastname: Wlodarski
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shaik
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.forename: Ramon V
authors.initials: RV
authors.lastname: Tiu
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
authors.forename: Christine L
authors.initials: CL
authors.lastname: O'Keefe
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007621:Karyotyping / Q000379:methods; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide