GRANULOCYTE-COLONY-STIMULATING FACTOR-INDUCED PROLIFERATION OF PRIMARY ADULT T-CELL LEUKEMIA-CELLS

Granulocyte-colony stimulating factor (G-CSF) is known to induce proli feration and differentiation of granulocyte progenitors, and is widely used to treat neutropenia induced by intensive chemotherapy for malig nant lymphoma or adult T-cell leukaemia/lymphoma (ATL), G-CSF is thoug ht not to stimulate malignant lymphoid cells, In the present study we examined the ability of G-CSF to induce in vitro growth of primary ATL cells from 14 patients (nine acute-type, two chronic-type and three l ymphoma-type), and we analysed the in vivo counts of ATL cells in pati ents who received G-CSF for neutropenia, FAGS analysis using phycoeryt hrin-labelled recombinant G-CSF demonstrated that ATL cells from 11/14 patients express some G-CSF receptor (G-CSFR), with a range between 5 .4% and 87.3%. Cells expressing G-CSFR also expressed CD4. Reverse pol ymerase chain reaction (PCR) analysis demonstrated expression of G-CSF R messenger RNA in G-CSFR expressing cells. Leukaemic cells derived fr om seven (four acute-type, one chronic-type and two lymphoma-type) of the 14 patients proliferated in vitro in response to G-CSF as measured by [H-3]thymidine incorporation; maximum responses were at G-CSF conc entrations of 10-100 ng/ml. Nine of 14 patients receiving rG-CSF for n eutropenia were analysed retrospectively for ATL cell numbers. Four pa tients whose primary tumour cells proliferated in response to rG-CSF i n vitro showed a significant increase in ATL cell count after administ ration of rG-CSF (P = 0.038), whereas five patients whose leukaemic ce lls did not proliferate in vitro showed no significant increase in ATL cell count. G-CSF can stimulate proliferation of ATL cells which may complicate therapy for this disease.