Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas.

Expert Opin Ther Targets 2018 01 24;22(1):45-57. Epub 2017 Nov 24.

a Institute of Animal Breeding and Genetics , University of Veterinary Medicine Vienna , Vienna , Austria.

Introduction: Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations in chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages. We summarize how these pathways might be interconnected in normal or cancer cells, which have lost differentiation capacity and drive oncogene transcription. Expert opinion: Due to similarities in driver mutations including epigenetic enzymes, JAK-STAT pathway activation and mutated checkpoint control through TP53, we hypothesize that similar therapeutic approaches could be of benefit in these diseases. We give an overview of how driver mutations in these malignancies contribute to hematopoietic cancer initiation or progression, and how these pathways can be targeted with currently available tools.

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Source
http://dx.doi.org/10.1080/14728222.2018.1406924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743003PMC
January 2018
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(Supplied by CrossRef)

Baker SG et al.
J Natl Cancer Inst 2015

Rosenfeld S et al.
Gene Regul Syst Bio 2011

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