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Masouleh, BK,Chevet, E,Panse, J,Jost, E,O'Dwyer, M,Bruemmendorf, TH,Samali, A
2015
July
Drugging the unfolded protein response in acute leukemias
Published
1
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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
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.
10.1186/s13045-015-0184-7
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