title: Drugging the unfolded protein response in acute leukemias.
abstract: The unfolded protein response (UPR), an endoplasmic reticulum (ER) stress-induced signaling cascade, is mediated by three major stress sensors IRE-1α, PERK, and ATF6α. 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.
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany. bkharabi@ukaachen.de.
authors.forename: Behzad
authors.initials: B
authors.lastname: Kharabi Masouleh
authors.affiliation: Université Rennes 1 - ER_440 "Oncogenesis, Stress & Signaling", Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Panse
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Jost
authors.affiliation: Apoptosis Research Centre (ARC), National University of Ireland, Galway, Ireland.|Department of Medicine, National University of Ireland, Galway, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: O'Dwyer
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Bruemmendorf
authors.affiliation: Apoptosis Research Centre (ARC), National University of Ireland, Galway, Ireland.|Department of Biochemistry, National University of Ireland, Galway, Ireland.
authors.forename: Afshin
authors.initials: A
authors.lastname: Samali
mesh_terms: D002470:Cell Survival; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000235:genetics*