Role of the spleen in cyclophosphamide-induced hematosuppression and extramedullary hematopoiesis in mice

Arch Med Res. 2009 May;40(4):249-55. doi: 10.1016/j.arcmed.2009.04.003. Epub 2009 Jun 4.

Abstract

Background and aims: Extramedullary hematopoiesis (EMH) is induced in spleens due to various diseases. The aim of this study is to investigate the role of spleen in cyclophosphamide (CTX)-induced hematosuppression and EMH in mice.

Methods: Balb/c mice were IP injected with 300 mg/kg CTX 2 weeks after splenectomy or sham operation and randomly sacrificed 1, 3, 7, 14, and 21 days after injection. Blood samples were collected, and spleens were weighed, histologically analyzed, and then used for flow cytometry.

Results: There were significant differences in white blood count, red blood count, platelet numbers and hemoglobin concentration between the splenectomized and sham-operated mice after CTX injection. The cellularity of the spleen was reduced 3 days following CTX treatment but then rose 7 days after CTX treatment. The numbers of colony-forming units in the spleen reached a peak 7 days after CTX injection, then declined. Flow cytometry demonstrated the percentage of CD34(+) and CD117(+) cells in the spleen increased 7 days after CTX injection, indicating the hematopoietic stem and progenitor cells in the spleen.

Conclusions: The study indicates that EMH occurs as a compensatory reaction to CTX-induced hematosuppression in the murine spleen, implying that conservation of the spleen may promote the recovery of cancer patients from chemotherapy-induced hematosuppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Cell Count
  • Cyclophosphamide / adverse effects*
  • Hematopoiesis / drug effects*
  • Hematopoiesis, Extramedullary / physiology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Proto-Oncogene Proteins c-kit / metabolism
  • Spleen / physiology*

Substances

  • Antigens, CD34
  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide
  • Proto-Oncogene Proteins c-kit