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Cancers (Basel). 2018 Mar 5;10(3). pii: E64. doi: 10.3390/cancers10030064.

The Role of Oncogenic Tyrosine Kinase NPM-ALK in Genomic Instability.

Author information

1
Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 5, 62500 Brno, Czech Republic. cosimo.lobello@ceitec.muni.cz.
2
Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 5, 62500 Brno, Czech Republic. vasileios.bikos@ceitec.muni.cz.
3
Department of Internal Medicine-Hematology and Oncology, University Hospital Brno, 62500 Brno, Czech Republic. janikova.andrea@fnbrno.cz.
4
Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 5, 62500 Brno, Czech Republic. sarka.pospisilova@ceitec.muni.cz.
5
Department of Internal Medicine-Hematology and Oncology, University Hospital Brno, 62500 Brno, Czech Republic. sarka.pospisilova@ceitec.muni.cz.

Abstract

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.

KEYWORDS:

ALK; DNA damage response; DNA repair; MutS protein homolog 2 (MSH2); NPM-ALK (nucleophosmin-anaplastic lymphoma kinase); anaplastic large cell lymphoma (ALCL); genomic instability; p53

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