Identification of New microRNA Biomarkers and Candidate Target Genes in Primitive CML Cells Using Global Comparative RNA analyses

• Published in: Blood 2014-12, Vol.124 (21), p.3133-3133
• Main Authors: Lin, Hanyang, Rothe, Katharina, Ruschmann, Jens, Petriv, Oleh, O’Neill, Kieran, Knapp, David J.H.F., Brinkman, Ryan R., Birol, Inanc, Forrest, Donna L., Hansen, Carl, Eaves, Connie J, Humphries, R. Keith, Jiang, Xiaoyan
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.3133.3133

Imatinib mesylate (IM) and other ABL tyrosine kinase inhibitors (TKIs) have had a major impact on early phase CML patient outcomes. However, they are rarely curative and initial and acquired TKI resistance remain challenges. This is attributed to the finding that chronic phase CML stem cells are innately more resistant to IM and other TKIs than the bulk of the more mature cells they generate. To identify differentially expressed and new miRNAs in CD34+ CML stem/progenitor cells that could be potential biomarkers and therapeutic targets, we used Illumina Deep Sequencing to obtain absolute miRNA expression profiles of highly purified CD34+ cells obtained at diagnosis from three CML patients who were classified retrospectively, after IM therapy, as IM-responders and three as IM-nonresponders. CD34+ cells isolated from five normal bone marrow (NBM) samples were similarly analyzed as controls. Bioconductor DESeq analysis revealed 63 differentially expressed miRNAs in the CD34+ cells from CML and NBM samples (P