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

被引:103
作者
Afable, Manuel G., II [1 ,2 ]
Wlodarski, Marcin [1 ,3 ]
Makishima, Hideki [1 ]
Shaik, Mohammed [1 ,2 ]
Sekeres, Mikkael A. [1 ,2 ]
Tiu, Ramon V. [1 ,2 ]
Kalaycio, Matt [2 ]
O'Keefe, Christine L. [1 ]
Maciejewski, Jaroslaw P. [1 ,2 ]
机构
[1] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44195 USA
[2] Cleveland Clin, Taussig Canc Inst, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44195 USA
[3] Univ Freiburg, Div Pediat Hematol & Oncol, Freiburg, Germany
关键词
UNIPARENTAL DISOMY; CYTOGENETIC ABNORMALITIES; ANTITHYMOCYTE GLOBULIN; COPY NUMBER; BONE-MARROW; CYCLOSPORINE; EVOLUTION; DIAGNOSIS; DISEASES; MDS/MPD;
D O I
10.1182/blood-2010-11-314393
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Blood. 2011;117(25):6876-6884)
引用
收藏
页码:6876 / 6884
页数:9
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