Transcriptional regulation of hematopoietic stem cell progenitors and acute myeloid leukemia by the IRE1a-XBP1 pathway [overexpression]

The inositol-requiring enzyme-1a (IRE1a), through its key effector transcription factor X-box binding protein-1 (XBP1), regulates cell fate and malignancy in a tissue and cell-specific manner. Here, we define the transcriptional perturbations associated with induction of XBP1 (encoded by the XBP1S gene generated by IRE1a) eficiency in patient derived human AML cells. Beyond its classical role in activating genes involved in restoring cellular proteostasis during the unfolded protein response (UPR), our transcriptome analysis reveal XBP1-dependent regulation of genes involved in diverse biological processes required for HSC homeostasis and acute myeloid leukemia (AML) development. Transcriptome of two patient-derived human AML cells (#41 and #88) transduced with control lentivirus (in triplicates, C1, C2 and C3) or XBP1 (X1, X2 and X3) were determined using TruSeq Stranded mRNA Libraries. The complete data set contains a total of 12 samples