title: Downregulation of neuropilin-1 in patients with acute myeloid leukemia treated with thalidomide.
abstract: OBJECTIVE
  Neuropilin-1 (NRP-1), a non-tyrosine kinase receptor functioning as a mediator of angiogenesis and neuronal guidance, was recently found to be significantly overexpressed in newly diagnosed acute myeloid leukemia (AML) patients with significant correlation to survival. The role of NRP-1 in refractory or relapsed AML patients and its regulation during anti-angiogenic treatment remain to be elucidated.
  
  
  METHODS
  Bone marrow biopsies of 10 patients with refractory or relapsed AML were evaluated for NRP-1 expression by immunohistochemical analysis, and NRP-1 expression level was determined before and after start of thalidomide therapy and correlated to response and growth factor expression.
  
  
  RESULTS
  NRP-1 expression was significantly increased in AML patients [median 7 arbitrary units (AU)] when compared with controls (n = 38, median 2.75 AU). Under thalidomide treatment, a marked difference in the course of NRP-1 expression between responders and non-responders was observed, however, without a statistical significance (P = 0.071) being reached. Additionally, a significant correlation of the NRP-1 expression level to microvessel density could be detected under treatment with thalidomide (P = 0.018).
  
  
  CONCLUSIONS
  Our data provide evidence of increased NRP-1 expression in relapsed or refractory AML. Additionally, our results suggest that thalidomide-induced antileukemic properties might at least in part be mediated by NRP-1 downregulation.
authors.affiliation: Department of Medicine/Hematology and Oncology, University of Muenster, Muenster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kreuter
authors.forename: Martin
authors.initials: M
authors.lastname: Steins
authors.forename: Katja
authors.initials: K
authors.lastname: Woelke
authors.forename: Thomas
authors.initials: T
authors.lastname: Buechner
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Mesters
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D042501:Angiogenic Proteins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D039942:Neuropilin-1 / Q000187:drug effects / Q000378:metabolism*; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D000970:Antineoplastic Agents; D039942:Neuropilin-1; D013792:Thalidomide