engleski

Notch signalling controls leukemic cells

The formation of new blood cells from hematopoietic stem cells is regulated by many factors on different levels. Among other, Notch and Ikaros family transcription factors play key role in differentiation of hematopoietic cells. Notch signalling pathway has been shown to regulate stem cells differentiation and loss of function experiments revealed that it is essential for the development of T cells as well as the Ikaros family transcription factors, Ikaros, Aiolos and Helios. A broader interest for Notch signaling araised by the discovery that the Notch gene is broken in T-cell acute leukemia. The human Notch signaling network consists of 4 receptors (Notch1-4) and 5 ligands, which are part of the Delta like (Dll1, 3, 4) and Jagged family ligands (Jagged 1, 2). For the functional pathway activation, three separate proteolytic steps are required, upon which releasement of the Notch intracellular domain (NICD) and translocation to the nucleus will occur. Activated Notch recruits DNA binding proteins, CSL (CBF/1&Supressor of hairless&Lag1), MAML (Mastermind like) and p300 to activate transcription of Notch target genes such as Hes1 (Hairy and enhancer-of-split 1) and Deltex1. It has been shown that Hes genes modulate the development of hematopoietic cells at multiple stages in mice. Maturation of lymphocytes is dependent on the level of Hes1 and Aiolos expression. However, their role in differentiation of the myeloid lineage remains vastly unexplored. The aim of this study was to investigate the influence of Notch and Ikaros family transcription factors on myelomonocytic differentiation.

B-CLL ; Notch

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