title: Alkyl phospholipid perifosine induces myeloid hyperplasia in a murine myeloma model.
abstract: OBJECTIVE
  Alkyl-lysophospholipids are a novel class of antitumor agents. Perifosine is a novel alkyl-lysophospholipid that can induce apoptosis in multiple myeloma (MM) tumor cells, both in vitro and in vivo. We investigated the effects of perifosine on the peripheral blood, bone marrow, and spleen of mice inoculated with subcutaneous plasmacytomas.
  
  
  METHODS
  Immunocompromised mice were inoculated with myeloma cell lines and treated with oral perifosine in either a daily or weekly schedule, or with vehicle only. When plasmacytomas reached 2 cm, mice were sacrificed. Terminal blood was analyzed with a Coulter counter, and counts were confirmed by light microscopy. Marrow and spleen were also analyzed by light microscopy.
  
  
  RESULTS
  In control mice, mean hemoglobin was 12 g/dL, white blood cell (WBC) count 7 x 10(9)/L, and mean platelet count was 292 x 10(9)/L. In contrast, the respective values for mice treated with perifosine weekly were 11 g/dL, 9 x 10(9)/L, and 944 x 10(9)/L; and for mice treated with perifosine daily were 10 g/dL, 11 x 10(9)/L, and 752 x 10(9)/L. The increase in WBCs was due, predominantly, to a neutrophilia. Compared to control mice, perifosine treatment induced marrow hypercellularity and splenic white pulp expansion.
  
  
  CONCLUSIONS
  These findings have clinical relevance because myeloid suppression is a dose-limiting toxicity of many cytotoxic agents, and myeloid hyperplasia is usually only observed in the setting of growth factor stimulation. Coupled with its remarkable in vitro MM cytotoxicity, these results strongly support the use of perifosine in clinical trials for patients with MM.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass., USA. laurence.catley@mater.org.au
authors.forename: Laurence
authors.initials: L
authors.lastname: Catley
authors.forename: Teru
authors.initials: T
authors.lastname: Hideshima
authors.forename: Dharminder
authors.initials: D
authors.lastname: Chauhan
authors.forename: Paola
authors.initials: P
authors.lastname: Neri
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Roderick
authors.initials: R
authors.lastname: Bronson
authors.forename: Weihua
authors.initials: W
authors.lastname: Song
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Tai
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D006965:Hyperplasia; D007964:Leukocytosis / Q000139:chemically induced; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology*; D022423:Myeloid Cells / Q000187:drug effects* / Q000473:pathology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013922:Thrombocytosis / Q000139:chemically induced
chemical_list: D010767:Phosphorylcholine; C105905:perifosine