title: Glucocorticoid and proteasome inhibitor impact on the leukemic lymphoblast: multiple, diverse signals converging on a few key downstream regulators.
abstract: Twenty years ago a proteasome inhibitor was suggested as therapy for glucocorticoid-resistant multiple myeloma, a disease that involves terminally differentiated B cells. Since then, research has proven that it has utility on a number of tumors resistant to chemotherapy. Hematologic malignancy, however, often involves lesser differentiated cells, which have a high potential to modulate their intrinsic machinery and thereby activate alternative rescue pathways. A corresponding multiplicity of therapies is not always practical. One approach to conditions with heterogeneous physiology is to identify key biochemical mediators, thereby reducing the number of treatment targets. Results from several ongoing studies indicate convergence of genomically diverse signal pathways to a limited number of key downstream regulators of apoptosis. Convergence of pathways can be exploited to address the problem of genetic heterogeneity in acute leukemia: this would mean treating multiple molecular aberrations with fewer drugs and enhanced therapeutic benefit.
authors.affiliation: Horemio Research Institute, First Department of Pediatrics, University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece.
authors.forename: George I
authors.initials: GI
authors.lastname: Lambrou
authors.forename: Lina
authors.initials: L
authors.lastname: Papadimitriou
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: Spiros A
authors.initials: SA
authors.lastname: Vlahopoulos
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D061988:Proteasome Inhibitors; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids; D061988:Proteasome Inhibitors; D011965:Receptors, Glucocorticoid