Downregulation of neuropilin-1 in patients with acute myeloid leukemia treated with thalidomide.
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.
Kreuter
Michael
M
Department of Medicine/Hematology and Oncology, University of Muenster, Muenster, Germany.
Steins
Martin
M
Woelke
Katja
K
Buechner
Thomas
T
Berdel
Wolfgang E
WE
Mesters
Rolf M
RM
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
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D000970:Antineoplastic Agents; D039942:Neuropilin-1; D013792:Thalidomide