Genome-wide profiling of miRNA associated with BCR-FGFR1 fusion kinase driven stem cell leukemia and lymphoma II

The BBC1 and BBC2 cell lines were isolated from pre-B-cell lymphoma models of a murine BCR-FGFR1 driven SCLL. miRNA profiles for BBC2 cells, were established using miRNA arrays. First, BBC2 cells were compared with FACS sorted, normal, murine splenic CD19+ B cells isolated from BALB/c mice, where upregulated and downregulated miRNAs in BBC2 cells were identified. We next investigated which of these miRNAs were affected by loss of FGFR1 function. Previously we showed that the FGFR inhibitor BGJ398 suppresses suppressed phosphoactivation of chimeric FGFR1 kinases. When BBC2 cells were treated with 50nM BGJ398 for 24 hours, up- and down-regulated miRNAs by FGFR1 signaling were identified. By comparasion of the two subsets of differentially expressed miRNAs, we were able to define core candidate miRNAs which appear to be regulated by BCR-FGFR1 in SCLL. The miRNA profiles of BBC2 cell sample treated with DMSO and BGJ398 were detected with miRNA microarray.