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

MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia

  1. Ramiro Garzon1,
  2. Stefano Volinia2,3,
  3. Chang-Gong Liu3,
  4. Cecilia Fernandez-Cymering3,
  5. Tiziana Palumbo3,
  6. Flavia Pichiorri3,
  7. Muller Fabbri3,
  8. Kevin Coombes4,
  9. Hansjuerg Alder3,
  10. Tatsuya Nakamura3,
  11. Neal Flomenberg5,
  12. Guido Marcucci1,
  13. George A. Calin6,
  14. Steven M. Kornblau7,
  15. Hagop Kantarjian8,
  16. Clara D. Bloomfield1,
  17. Michael Andreeff7, and
  18. Carlo M. Croce3
  1. 1Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, Ohio State University, Columbus;
  2. 2DAMA, Data Mining of DNA Microarrays, University of Ferrara, Ferrara, Italy;
  3. 3Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus;
  4. 4Biostatistics Division, M. D. Anderson Cancer Center, Texas State University, Houston;
  5. 5Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA;
  6. 6Experimental Therapeutics & Cancer Genetics,
  7. 7Section of Molecular Hematology and Therapy, Department of Blood and Bone Marrow Transplantation, and
  8. 8Department of Leukemia, M. D. Anderson Cancer Center, Texas State University, Houston
  1. Presented in part in abstract form at the 48th annual meeting of the American Society of Hematology, Orlando, FL, December 11, 2006: abstract 152.

Abstract

MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are negative regulators of gene expression. To determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in acute myeloid leukemia (AML), we evaluated the miRNA expression of CD34+ cells and 122 untreated adult AML cases using a microarray platform. After background subtraction and normalization using a set of housekeeping genes, data were analyzed using Significance Analysis of Microarrays. An independent set of 60 untreated AML patients was used to validate the outcome signatures using real-time polymerase chain reaction. We identified several miRNAs differentially expressed between CD34+ normal cells and the AML samples. miRNA expression was also closely associated with selected cytogenetic and molecular abnormalities, such as t(11q23), isolated trisomy 8, and FLT3-ITD mutations. Furthermore, patients with high expression of miR-191 and miR-199a had significantly worse overall and event-free survival than AML patients with low expression (overall survival: miR-191, P = .03; and miR-199a, P = .001, Cox regression). In conclusion, miRNA expression in AML is closely associated with cytogenetics and FLT3-ITD mutations. A small subset of miRNAs is correlated with survival.

  • Submitted July 2, 2007.
  • Accepted December 30, 2007.
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