SNP array-based karyotyping: differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes. | Aplastic Anemia and MDS International Foundation

SNP array-based karyotyping: differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes.

Journal Title: 
Blood
Author(s): 
Afable MG 2nd, Wlodarski M, Makishima H, Shaik M, Sekeres MA, Tiu RV, Kalaycio M, O'Keefe CL, Maciejewski JP
Primary Author: 
Afable MG 2nd
Original Publication Date: 
Thursday, April 28, 2011

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 (SNP) arrays, complementing routine cytogenetics. We hypothesized that clinically important cryptic clonal aberrations may exist in some patients with bone marrow failure. Combined metaphase and SNP array 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 3/93 patients with AA. In hMDS, additional clonal lesions were detected in 5/14 (36%) patients with normal/non-informative routine cytogenetics. In a subset of AA patients studied at presentation, persistent chromosomal genomic lesions were found in 10/33, suggesting that the initial diagnosis may have been hMDS. Similarly, using SNP arrays, earlier clonal evolution was found in 4/7 of AA patients followed serially. In sum, our results indicate that SNP arrays identify cryptic clonal genomic aberrations in AA and hMDS leading to improved distinction of these disease entities.