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

Ann-Kathrin Eisfeld, Guido Marcucci, Kati Maharry, Sebastian Schwind, Michael D. Radmacher, Deedra Nicolet, Heiko Becker, Krzysztof Mrózek, Susan P. Whitman, Klaus H. Metzeler, Jason H. Mendler, Yue-Zhong Wu, Sandya Liyanarachchi, Ravi Patel, Maria R. Baer, Bayard L. Powell, Thomas H. Carter, Joseph O. Moore, Jonathan E. Kolitz, Meir Wetzler, Michael A. Caligiuri, Richard A. Larson, Stephan M. Tanner, Albert de la Chapelle and Clara D. Bloomfield


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.