title: High expression of IGFBP2 is associated with chemoresistance in adult acute myeloid leukemia.
abstract: Insulin-like growth factor (IGF) signaling plays an important role in many tumors and overexpression of IGF Binding Protein (IGFBP) 2 has been associated with adverse outcome in childhood leukemia. Here, we evaluated IGFBP2 mRNA expression and its prognostic implications in 99 adult acute myeloid leukemia (AML) patients by quantitative real-time RT-PCR. High IGFBP2 was associated with a high incidence of primary resistant disease (IGFBP2 high 65%, IGFBP2 low 32%; P=0.02) and was independently predictive for therapy resistance [OR 3.6 (95% CI 1.2-11); P=0.02] in multivariate analyses. Gene-expression profiling revealed an up-regulation of genes implicated in leukemogenesis (MYB, MEIS1, HOXB3, HOXA9) and genes associated with adverse outcome (ERG, WT1) in patients with high IGFBP2 expression. Thus, our data suggest a role of IGFBP2 and IGF signaling in chemoresistance of AML. Patients with high IGFBP2 expression might benefit from molecular therapies targeting the IGF pathway.
authors: Department of Hematology and Oncology, Charité University Hospital, Campus Benjamin Franklin, Berlin, Germany. andrea.kuehnl@charite.de
authors: Andrea
authors: A
authors: Kühnl
authors: Martin
authors: M
authors: Kaiser
authors: Martin
authors: M
authors: Neumann
authors: Lars
authors: L
authors: Fransecky
authors: Sandra
authors: S
authors: Heesch
authors: Michael
authors: M
authors: Radmacher
authors: Guido
authors: G
authors: Marcucci
authors: Clara D
authors: CD
authors: Bloomfield
authors: Wolf-Karsten
authors: WK
authors: Hofmann
authors: Eckhard
authors: E
authors: Thiel
authors: Claudia D
authors: CD
authors: Baldus
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013002:Somatomedins / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D013002:Somatomedins