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Crosstalk between Notch and PARP pathways in lymphocytes

Notch signaling pathway is one of the main pathways directing different developmental processes, as its outcome also depends on cellular response and presence of interacting molecules. In hematopoietic cells, Notch has an important role in lymphocyte development. In this study, the aim was to analyze Notch signalization in different types of leukemia lymphocytes and the influence of poly(ADP-ribose) polymerase (PARP) activity on this process. PARP is an enzyme involved in DNA damage repair, posttranslational modification of transcription factors and chromatin structure changes. B and T leukaemia cells were treated with Notch (DAPT) and PARP (PJ-34) inhibitors, alone or in combination, for a prolonged period of time. All three types of cell lines showed high viability under the treatment and continued to proliferate. Analysis of gene and protein expression panel, involved in Notch and PARP pathways, showed ligand JAGGED1 expression increase after PARP1 inhibition in B cell lines and changes in Ikaros family members in both, B and T cell lines, regardless of the Notch signalling activity, after γ-secretase inhibition (DAPT). These data indicate that Notch and PARP inhibition, although not initiating differentiation in leukaemia cells analysed, induce changes in signalling circuits and chromatin modelling factors.

Notch ; PARP ; lymphocytes ; leukemia

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