WITHDRAWN: Expression profiles and biological implications of plasma miRNAs associated with chronic myeloid leukemia phases

Abstract

ABSTRACTmicroRNAs play important regulatory roles in hematologic malignancies, and dysregulation of circulating miRNAs serves as diagnostic, prognostic and predictive biomarkers in many diseases. The correlation of plasma miRNA profiles with the progression of chronic myeloid leukemia (CML) has not been investigated. We have applied microarrays to identify differentially expressed miRNAs, followed by qRT-PCR to validate candidate miRNAs from four sample pools including chronic phase (CP), accelerated phase(AP), blast crisis(BC) and healthy control. Clustering analyses revealed varying phase-specific patterns of plasma miRNA expression during CML progression. Different phases of CML showed differential expression profiles between sample pools during the progression. The functional annotation tool, DAVID, found that putative targets of dysregulated miRNAs in different phases of diease are involved in several important signaling pathways. Gradually decreased expression levels of miR-451a were validated in CML patients from the CP to AP and BC; when CML patients achieved major molecular response (MMR), miR-451a expression was increased and restored to normal range. These data provide an important resource for studies on CML progression and allow a better understanding of the fundamental differences in plasma miRNA expression profiles among the different phases of CML.