Granulocyte-colony stimulating factor-induced proliferation of primary adult T-cell leukaemia cells

Br J Haematol. 1997 Mar;96(4):715-23. doi: 10.1046/j.1365-2141.1997.d01-2102.x.

Abstract

Granulocyte-colony stimulating factor (G-CSF) is known to induce proliferation and differentiation of granulocyte progenitors, and is widely used to treat neutropenia induced by intensive chemotherapy for malignant lymphoma or adult T-cell leukaemia/lymphoma (ATL). G-CSF is thought 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 lymphoma-type), and we analysed the in vivo counts of ATL cells in patients who received G-CSF for neutropenia. FACS analysis using phycoerythrin-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 polymerase chain reaction (PCR) analysis demonstrated expression of G-CSFR messenger RNA in G-CSFR expressing cells. Leukaemic cells derived from 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 [3H]thymidine incorporation; maximum responses were at G-CSF concentrations of 10-100 ng/ml. Nine of 14 patients receiving rG-CSF for neutropenia were analysed retrospectively for ATL cell numbers. Four patients whose primary tumour cells proliferated in response to rG-CSF in vitro showed a significant increase in ATL cell count after administration of rG-CSF (P = 0.038), whereas five patients whose leukaemic cells 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Division / drug effects
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Leukemia, T-Cell / pathology*
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / drug therapy*
  • RNA, Messenger / analysis

Substances

  • RNA, Messenger
  • Granulocyte Colony-Stimulating Factor