Genomic stability is crucial for cell life and transmitting genetic material is one of the primary tasks of the cell. The cell needs to be able to recognize any possible error and quickly repair it, and thus, cells have developed several mechanisms to detect DNA damage and promote repair during evolution. The DNA damage response (DDR) and DNA repair pathways ensure the control of possible errors that could impair the duplication of genetic information and introduce variants in the
DNA. Endogenous and exogenous factors compromise
genomic stability and cause dysregulation in the DDR and DNA repair pathways.
Cancer cells often impair these mechanisms to overcome cellular barriers (cellular senescence and/or apoptosis), leading to
malignancy. NPM (
nucleophosmin)-ALK (
anaplastic lymphoma kinase) is an oncogenic
tyrosine kinase that is involved in the development of
anaplastic large cell lymphoma (ALCL).
NPM-ALK is known to be involved in the activation of proliferative and anti-apoptotic signaling pathways. New evidence reveals that
NPM-ALK translocation also impairs the ability of cells to maintain the
genomic stability through both DDR and DNA repair pathways. This review aims to highlight the role of the oncogenic
tyrosine kinase NPM-ALK in the cell, and pointing to new possible therapeutic strategies.