Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Ramon V. Tiu1,
  2. Lukasz P. Gondek1,
  3. Christine L. O'Keefe1,
  4. Paul Elson2,
  5. Jungwon Huh3,
  6. Azim Mohamedali4,
  7. Austin Kulasekararaj4,
  8. Anjali S. Advani5,
  9. Ronald Paquette6,
  10. Alan F. List7,
  11. Mikkael A. Sekeres5,
  12. Michael A. McDevitt8,
  13. Ghulam J. Mufti4, and
  14. Jaroslaw P. Maciejewski1,*
  1. 1 Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, United States;
  2. 2 Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States;
  3. 3 Laboratory Medicine, Ewha Womans University, School of Medicine, Seoul, Korea, Republic of;
  4. 4 Department of Haematological Medicine, King's College London School of Medicine, London, United Kingdom;
  5. 5 Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute Center, Cleveland Clinic, Cleveland, Ohio, United States;
  6. 6 Department of Medicine, University of California at Los Angeles Medical Center, Los Angeles, California, United States;
  7. 7 Immunology Program and Malignant Hematology Program, Moffitt Cancer Center and Research Institute, Tampa, Florida, United States;
  8. 8 Divisions of Hematology and Hematological Malignancy, Departments of Internal Medicine and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  1. * Corresponding author; email: maciejj{at}


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.