Long-read isoform expression profiles modulated by HES4 transcription factor in established human T-cell leukemias

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy characterized by an expansion of T-cell progenitors and DNA mutations that lead to an overactive NOTCH1 signaling in over 50% of T-ALL cases. Even though intracellular Notch1(ICN1) can modulate the target gene expression as a monomer, homodimerization of ICN1 is indispensable for the leukemogenesis of mouse T-cells. Hes4 is a direct target of Notch1 dimerization in human T-ALL. To investigate the impact on human transcriptional variants of HES4 expression in T-ALL cell lines, we performed a gene expression profiling by PacBio long-read isoform sequencing (Iso-Seq) in the human DND41 and T-ALL1 cell lines after transduction with HES4 or empty lentivectors, and with shScramble or shHES4 lentivectors, respectively.