Involvement of granulocyte colony-stimulating factor in proliferation of adult T-cell leukemia cells.

Granulocyte-colony stimulating factor (G-CSF) was originally found to induce proliferation and differentiation of normal granulocyte progenitors. Recent studies demonstrated that G-CSF induces growth of some malignant cells, including lymphoid cells. G-CSF is now widely and successfully used to treat neutropenia induced by intensive chemotherapy, and the responsive growth of malignant cells becomes a major clinical issue. Adult T-cell leukemia (ATL) is a malignant lymphoid disease of T cells, etiologically associated with human T cell lymphotropic virus type I (HTLV-I). We demonstrated that primary ATL cells in about 80% of patients expressed cell surface G-CSF receptor (G-CSFR). Our recent data also show that ATL cells from a third of the patients show responsive growth to G-CSF ex vivo. Several patients whose ATL cells proliferated in response to G-CSF showed a significant increase of the ATL cell count after administration of G-CSF in vivo. These observations suggest caution for it's routine clinical use in ATL. The molecular mechanism of G-CSF responsive growth of ATL cells is obscure, however the population of G-CSFR expressing cells is larger in responsive cases than in nonresponsive cases. Expression of G-CSFR on ATL cells may relate to the expression of Tax protein encoded by HTLV-I. Precise studies on G-CSFR signaling in ATL cells are necessary for the safe use of G-CSF routinely for ATL patients.