Differential action of diffusible molecules in long‐term marrow culture on proliferation of leukaemic and normal haemopoietic cells

Frank C. Firkin, Raquella Birner, Sherif Farag

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Summary. The capacity of diffusible molecules in the fluid phase of long‐term human bone marrow culture (LTMC) to exert preferential adverse effects on leukaemic relative to normal haemopoietic cells has been investigated. Responses of isolated cell populations were assessed in diffusion chamber inserts which permitted contact with fluid phase molecules but not with the adherent stromal cell layer of the LTMC system. Growth of AML cells in diffusion chambers was inhibited during co‐culture with LTMC of autologous leukaemic bone marrow, and the same effect was produced during co‐culture with normal LTMC. No inhibitory action was exerted on growth of normal haemopoietic precursors under the same conditions. Comparable responses were observed with human leukaemic cell lines and patient leukaemic cells, and studies on cell lines demonstrated inhibition of growth was induced by molecules generated in LTMC which caused accumulation in G1 phase of leukaemic cells of both myeloid and lymphoid lineage. The inhibitory effect was not reproduced by TGFβ, IFNγ, IFNα, TNFα, LIF, SCF or II‐6, and was not impaired by inhibitors of nitric oxide or PGE production in the LTMC. These observations suggest the action of diffusible molecules of undefined constitution contributes to the preferential loss of leukaemic cells in LTMC.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalBritish journal of haematology
Volume84
Issue number1
DOIs
StatePublished - May 1993
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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