Correlation or reciprocity of Notch and Aiolos in Leukemia

Notch signaling pathway is highly conserved during evolution and critical for cell development. Leukemia cells have the associating characteristic of hematopoietic cells being blocked in the progression of differentiation to their mature form. It has been shown that Notch receptors and ligands in the immune system affect hematopoietic stem cells as well lymphocyte precursors. Notch guides lineage specification, cell progression, commitment and survival and deregulation of this pathway has been shown to be involved in either the occurrence or in the progression of T-cell acute lymphoblastic leukemia, as historically known, but also in other types of leukemia of B cell origin like B-cell chronic lymphocytic leukemia (B CLL). Its role has also been studied in myelopoiesis and myeloid leukemia. In addition to Notch, the Ikaros family of zinc - finger proteins, Ikaros, Aiolos and Helios are crucial for the development of lymphocytes. By acting as chromatin remodeling transcription factors they influence gene expression and guide the differentiation pathways of lymphocytes. Another layer of complexity to the story of differentiation is added when we take into account the various isoforms of proteins in the Ikaros family and the homo- and heterodimers the proteins in the pathway form. We and others have previously shown an elevated expression of Aiolos in CLL patients. The aim of the present study is to compare the mRNA and protein expression of Notch, Ikaros family members, especially Aiolos, and their downstream regulators to better understand their implication in leukemia. Considering the importance of the Notch pathway and the proteins involved, elucidating sequential steps from stem cells to mature immunocompetent cells will pave the way for better and more efficient treatments, as well as help us understand the regular task of these proteins in lymphocyte development.