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New lesions detected by single nucleotide polymorphism array-based chromosomal analysis have important clinical impact in acute myeloid leukemia

Title
New lesions detected by single nucleotide polymorphism array-based chromosomal analysis have important clinical impact in acute myeloid leukemia
Authors
Tiu R.V.Gondek L.P.O'Keefe C.L.Huh J.Sekeres M.A.Elson P.McDevitt M.A.Wang X.F.Levis M.J.Karp J.E.Advani A.S.Maciejewski J.P.
Ewha Authors
허정원
SCOPUS Author ID
허정원scopus
Issue Date
2009
Journal Title
Journal of Clinical Oncology
ISSN
0732-183XJCR Link
Citation
vol. 27, no. 31, pp. 5219 - 5226
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Purpose: Cytogenetics is the primary outcome predictor in acute myeloid leukemia (AML). Metaphase cytogenetics (MC) detects an abnormal karyotype in only half of patients with AML, however. Single nucleotide polymorphism arrays (SNP-A) can detect acquired somatic uniparental disomy (UPD) and other cryptic defects, even in samples deemed normal by MC. We hypothesized that SNP-A will improve detection of chromosomal defects in AML and that this would enhance the prognostic value of MC. Patients and Methods: We performed 250K and 6.0 SNP-A analyses on 140 patients with primary (p) and secondary (s) AML and correlated the results with clinical outcomes and Flt-3/nucleophosmin (NPM-1) status. Results: SNP-A is more sensitive than MC in detecting unbalanced lesions (pAML, 65% v 39%, P = .002; and sAML, 78% v 51%, P = .003). Acquired somatic UPD, not detectable by MC, was common in our AML cohort (29% in pAML and 35% in sAML). Patients with SNP-A lesions including acquired somatic UPD exhibited worse overall survival (OS) and event-free survival (EFS) in pAML with normal MC and in pAML/sAML with abnormal MC. SNP-A improved the predictive value of Flt-3 internal tandem duplication/NPM-1 status, with inferior survival seen in patients with additional SNP-A defects. Multivariate analyses confirmed the independent predictive value of SNP-A defects for OS (hazard ratio [HR] = 2.52; 95% CI, 1.29 to 5.22; P = .006) and EFS (HR = 1.72; 95% CI, 1.12 to 3.48; P = .04). Conclusion: SNP-A analysis allows enhanced detection of chromosomal abnormalities and provides important prognostic impact in AML. © 2009 by American Society of Clinical Oncology.
DOI
10.1200/JCO.2009.21.9840
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의학전문대학원 > 의학과 > Journal papers
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