Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies

Ramon V. Tiu, Lukasz P. Gondek, Christine L. O'Keefe, Paul Elson, Jungwon Huh, Azim Mohamedali, Austin Kulasekararaj, Anjali S. Advani, Ronald Paquette, Alan F. List, Mikkael A. Sekeres, Michael A. McDevitt, Ghulam J. Mufti and Jaroslaw P. Maciejewski


Single nucleotide polymorphism arrays (SNP-A) have emerged as an important tool in the identification of chromosomal defects undetected by metaphase cytogenetics (MC) in hematologic cancers, offering superior resolution of unbalanced chromosomal defects and acquired copy-neutral loss of heterozygosity. Myelodysplastic syndromes (MDS) and related cancers share recurrent chromosomal defects and molecular lesions that predict outcomes. We hypothesized that combining SNP-A and MC could improve diagnosis/prognosis and further the molecular characterization of myeloid malignancies. We analyzed MC/SNP-A results from 430 patients (MDS=250, MDS/MPN=95, AML from MDS=85). The frequency and clinical significance of genomic aberrations was compared between MC and MC plus SNP-A. Combined MC/SNP-A karyotyping lead to higher diagnostic yield of chromosomal defects (74 vs. 44%, p=<0.0001), compared to MC alone, often through detection of novel lesions in patients with normal/non-informative (54%) and abnormal (62%) MC results. Newly detected SNP-A defects contributed to poorer prognosis for patients stratified by current morphologic and clinical risk schemes. The presence and number of new SNP-A detected lesions are independent predictors of overall and event free survival. The significant diagnostic and prognostic contribution of SNP-A-detected defects in MDS and related diseases underscores the utility of SNP-A when combined with MC in hematologic malignancies.

  • Submitted July 14, 2010.
  • Accepted December 24, 2010.