title: Disease-stabilizing treatment with all-trans retinoic acid and valproic acid in acute myeloid leukemia: serum hsp70 and hsp90 levels and serum cytokine profiles are determined by the disease, patient age, and anti-leukemic treatment.
abstract: Heat shock protein (HSP) 70 and HSP90 are released by primary human acute myeloid leukemia (AML) cells during stress-induced spontaneous in vitro apoptosis. The AML cells also show constitutive release of several cytokines and the systemic serum levels of several soluble mediators are altered in patients with untreated AML. In the present study, we have investigated serum levels of HSP70/HSP90 and the serum cytokine profiles of patients with untreated AML and patients receiving AML-stabilizing palliative treatment based on all-trans retinoic acid (ATRA) plus valproic acid. Patients with untreated AML showed increased HSP90 levels and a distinct serum cytokine profile when compared with healthy controls, and low pre-therapy HSP90 levels were associated with a prolonged survival during treatment with ATRA + valproic acid + theophyllin. Hierarchical cluster analysis showed a close association between HSP70, HSP90, IL-1 receptor antagonist (IL-1ra), and hepatocyte growth factor (HGF) levels. Furthermore, disease-stabilizing therapy altered the serum-cytokine profile, but the correlations between HSP70/HSP90/IL-1ra/HGF were maintained only when ATRA + valproic acid were combined with theophyllin but not when combined with cytarabine. We conclude that both HSP levels and serum cytokine profiles are altered and may represent possible therapeutic targets or prognostic markers in human AML.
authors.affiliation: Section for Hematology, Institute of Medicine, University of Bergen, Bergen, Norway. hanne.fredly@med.uib.no
authors.forename: Hanne
authors.initials: H
authors.lastname: Fredly
authors.forename: Håkon
authors.initials: H
authors.lastname: Reikvam
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
authors.forename: Oystein
authors.initials: O
authors.lastname: Bruserud
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage; D016207:Cytokines / Q000097:blood*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000097:blood*; D018841:HSP90 Heat-Shock Proteins / Q000097:blood*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D015479:Leukemia, Myelomonocytic, Acute / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D010166:Palliative Care; D011379:Prognosis; D013806:Theophylline / Q000008:administration & dosage; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D009363:Neoplasm Proteins; D003561:Cytarabine; D014212:Tretinoin; D014635:Valproic Acid; D013806:Theophylline