Drugging the unfolded protein response in acute leukemias
Kharabi Masouleh, Behzad Chevet, Eric Panse, Jens Jost, Edgar O’Dwyer, Michael Bruemmendorf, Tim H. Samali, Afshin
Kharabi Masouleh, Behzad
Chevet, Eric
Panse, Jens
Jost, Edgar
O’Dwyer, Michael
Bruemmendorf, Tim H.
Samali, Afshin
Publication Date
2015-07-16
Keywords
acute myeloid leukemia, acute lymphoblastic leukemia, leukemia stem cells, unfolded protein response, xbp1, small-molecule inhibitors, acute myeloid-leukemia, endoplasmic-reticulum stress, acute lymphoblastic-leukemia, acute promyelocytic leukemia, acute myelogenous leukemia, xbp1 messenger-rna, induced cell-death, cancer stem-cells, pml-rar-alpha, er stress
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Article
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Kharabi Masouleh, Behzad; Chevet, Eric; Panse, Jens; Jost, Edgar; O’Dwyer, Michael; Bruemmendorf, Tim H. Samali, Afshin (2015). Drugging the unfolded protein response in acute leukemias. Journal of Hematology & Oncology 8 ,
Abstract
The unfolded protein response (UPR), an endoplasmic reticulum (ER) stress-induced signaling cascade, is mediated by three major stress sensors IRE-1 alpha, PERK, and ATF6 alpha. Studies described the UPR as a critical network in selection, adaptation, and survival of cancer cells. While previous reviews focused mainly on solid cancer cells, in this review, we summarize the recent findings focusing on acute leukemias. We take into account the impact of the underlying genetic alterations of acute leukemia cells, the leukemia stem cell pool, and provide an outline on the current genetic, clinical, and therapeutic findings. Furthermore, we shed light on the important oncogene-specific regulation of individual UPR signaling branches and the therapeutic relevance of this information to answer the question if the UPR could be an attractive novel target in acute leukemias.
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Publisher
Springer Nature
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Attribution-NonCommercial-NoDerivs 3.0 Ireland