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

miR-3151 interplays with its host gene BAALC and independently impacts on outcome of patients with cytogenetically normal acute myeloid leukemia

  1. Ann-Kathrin Eisfeld1,
  2. Guido Marcucci1,
  3. Kati Maharry2,
  4. Sebastian Schwind1,
  5. Michael D. Radmacher1,
  6. Deedra Nicolet1,
  7. Heiko Becker1,
  8. Krzysztof Mrózek1,
  9. Susan P. Whitman1,
  10. Klaus H. Metzeler1,
  11. Jason H. Mendler1,
  12. Yue-Zhong Wu1,
  13. Sandya Liyanarachchi1,
  14. Ravi Patel1,
  15. Maria R. Baer3,
  16. Bayard L. Powell4,
  17. Thomas H. Carter5,
  18. Joseph O. Moore6,
  19. Jonathan E. Kolitz7,
  20. Meir Wetzler8,
  21. Michael A. Caligiuri1,
  22. Richard A. Larson9,
  23. Stephan M. Tanner1,
  24. Albert de la Chapelle1, and
  25. Clara D. Bloomfield1,*
  1. 1 The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States;
  2. 2 Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN, United States;
  3. 3 Greenbaum Cancer Center, University of Maryland, Baltimore, MD, United States;
  4. 4 Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, United States;
  5. 5 University of Iowa, Iowa City, IA, United States;
  6. 6 Duke University Medical Center, Durham, NC, United States;
  7. 7 Monter Cancer Center, Hofstra North Shore-Long Island Jewish School of Medicine, Lake Success, NY, United States;
  8. 8 Roswell Park Cancer Institute, Buffalo, NY, United States;
  9. 9 University of Chicago Medical Center, Chicago, IL, United States
  1. * Corresponding author; email: clara.bloomfield{at}osumc.edu

Abstract

High BAALC expression levels associate with poor outcome in cytogenetically normal AML (CN-AML) patients. Recently, microRNA miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene- (GEP) and microRNA-expression (MEP) profiling was performed using microarrays. High miR-3151 expression associated with shorter disease-free and overall survival, while high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In GEP high miR-3151 expressers showed downregulation of genes involved in transcriptional regulation, post-translational modification and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. In conclusion, high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and impacts on different outcome endpoints than its host gene BAALC. The combination of both markers identified a patient subset with the poorest outcome. The described interplay of an intronic miR and its host may have important biologic implications.

  • Submitted February 2, 2012.
  • Accepted March 26, 2012.