Transcription factors involved in drug resistance in acute lymphoblastic leukemia

The efficacy of glucocorticoid receptor modulation is well established in Acute Lymphoblastic Leukemia(ALL) but the response remains heterogeneous and limited by emergence of drug resistance. Here we use, two clonally-derived cell lines (CEM-C1 and CEM-C7) from a 3-year-old T-cell ALL patient, as a model system to understand the mechanisms of drug resistance in these cell lines; the clone CEM-C1 is resistant to dexamethasone-induced apoptosis and CEM-C7 is sensitive. We performed ATACseq and RNAseq to query for TF binding motifs present in the open regions of the chromatin and expression levels of TFs that could recognize the identified motifs. We are experimentally validating our hypothesis that depletion of the TFs identified, either singly or in combination, in CEM-C7 cells will cause dexamethasone resistance in CEM-C7 cells. Map the hypersensitve regions in ALL sensitive and resistant cell lines. Identfy TF motifs that underlie the diffrentially accesible regions. Perform RNAseq to get the expression data for TF candidates. We have 7 ATAC libaries and 6 RNAseq libraries. Libraries were sequenced paired end (2x75).