Adverse prognostic impact of abnormal lesions detected by genome-wide single nucleotide polymorphism array-based karyotyping analysis in acute myeloid leukemia with normal karyotype

J Clin Oncol. 2011 Dec 10;29(35):4702-8. doi: 10.1200/JCO.2011.35.5719. Epub 2011 Nov 14.

Abstract

Purpose: This study attempted to analyze the prognostic role of single nucleotide polymorphism array (SNP-A) -based karyotying in 133 patients with acute myeloid leukemia with normal karyotype (AML-NK), which presents with diverse clinical outcomes, thus requiring further stratification of patient subgroups according to their prognoses.

Patients and methods: A total of 133 patients with AML-NK confirmed by metaphase cytogenetics (MC) and fluorescent in situ hybridization analysis were included in this study. Analysis by Genome-Wide Human SNP 6.0 Array was performed by using DNAs derived from marrow samples at diagnosis.

Results: Forty-three patients (32.3%) had at least one abnormal SNP lesion that was not detected by MC. One hundred thirteen abnormal SNP lesions included 55 losses, 23 gains, and 35 copy-neutral losses of heterozygosity. Multivariate analyses showed that detection of abnormal SNP lesions by SNP-A karyotyping results in an unfavorable prognostic value for overall survival (hazard ratio [HR], 2.69; 95% CI, 1.50 to 4.82; P = .001); other significant prognostic factors included secondary AML (HR, 5.55; 95% CI, 1.80 to 17.14; P = .003), presence of the FLT3 mutation (HR, 3.17; 95% CI, 1.71 to 5.87; P < .001), and age (HR, 1.03; 95% CI, 1.01 to 1.05; P = .020).

Conclusion: Our data demonstrated that abnormal SNP lesions detected by SNP-A karyotyping might indicate an adverse prognosis in patients with AML-NK, thus requiring a more sophisticated treatment strategy for improvement of treatment outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Genome, Human
  • Humans
  • Karyotyping / methods*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Treatment Outcome
  • Young Adult