FGF-2 reduces SDF-1

Bethesda, MD -

Numerous types of leukemias are associated with secretion of the cytokine fibroblast growth factor-2 (FGF-2). These leukemias are also associated with splenomegaly, hepatomegaly, and extramedullary hematopoiesis.

In a recent paper (Nakayama et al. Effect of fibroblast growth factor 2 on stromal cell-derived factor 1 production by bone marrow stromal cells and hematopoiesis. J Natl Cancer Inst. 2007 Feb 7;99(3):223-35.) the effects of FGF-2 on induction of extramedullary hematopoiesis were examined.

The investigators noticed that treatment of stromal cells with FGF-2 resulted in a decreased production of stromal derived factor-1 (SDF-1). Since SDF-1 is responsible for the localization and retention of bone marrow hematopoietic stem cells in the bone marrow compartment, it is reasonable to believe that by decreasing the amount of SDF-1 produced that FGF-2 may be responsible for the release of hematopoietic stem cells from the bone marrow compartment and entry into non-bone marrow anatomical niches.

In order to conclusively demonstrate this, the investigators treated mice in vivo with FGF-2. In agreement with the hypothesis of the experiment, mice treated with FGF-2 had increased extramedullary hematopoieisis and reduced retention of bone marrow hematopoietic stem cells in the bone marrow compartment.

This paper is interesting since there are patents that teach systemic administration of FGF-2 may be useful for the treatment of hematopoietic dysfunction. This paper points out a problem with this approach.