Related Experiment Video
Updated: Jul 14, 2026
A Human Peripheral Blood Mononuclear Cell (PBMC) Engrafted Humanized Xenograft Model for Translational Immuno-oncology (I-O) Research
Published on: August 15, 2019
Alkyl phospholipid perifosine induces myeloid hyperplasia in a murine myeloma model
Laurence Catley1, Teru Hideshima, Dharminder Chauhan
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass., USA. laurence.catley@mater.org.au
Objectives:
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.
Insights
Perifosine, an alkyl-lysophospholipid, promotes white blood cell production and bone marrow activity in mice with multiple myeloma. This suggests potential for treating myeloid suppression in cancer patients.
Area of Science:
- Pharmacology
- Oncology
- Hematology
Background:
- Alkyl-lysophospholipids represent a novel class of antitumor agents.
- Perifosine demonstrates in vitro and in vivo apoptosis induction in multiple myeloma (MM) cells.
Purpose of the Study:
- To investigate the effects of perifosine on peripheral blood, bone marrow, and spleen in mice with plasmacytomas.
Main Methods:
- Immunocompromised mice bearing myeloma cell lines were treated with oral perifosine (daily or weekly) or vehicle.
- Terminal blood, bone marrow, and spleen analyses were performed using a Coulter counter and light microscopy.
Main Results:
- Perifosine treatment led to increased white blood cell (WBC) counts, primarily neutrophilia, and elevated platelet counts compared to controls.
- Mice treated with perifosine exhibited marrow hypercellularity and splenic white pulp expansion.
Conclusions:
- Perifosine induces myeloid hyperplasia, contrasting with the myeloid suppression typical of cytotoxic agents.
- These findings support the clinical investigation of perifosine for multiple myeloma patients, particularly given its MM cytotoxicity and potential to mitigate myeloid suppression.
