ras oncogene mediates paracrine interactions between leukemic progenitor cells and stromal elements

H. Guenter Derigs, Theresa S. Nahreini, Maureen Harrington, Gem S. Burgess, Denis English, Lowell Inhorn, Debra Klingberg, Theodore G. Gabig, H. Boswell

Research output: Chapter in Book/Report/Conference proceedingChapter


Our interest in the role of paracrine interactions detennining the outcome of early leukemic cell growth was founded on our observations with coincubation of the growth factor-dependent immortal myeloid cell line, FDC-Pl, on long-tenn marrow culture stromal layers devoid of ongoing hemopoiesis, I as described in the previous chapter. In those studies we utilized long-tenn marrow culture stromal laers that were depleted of endogenous hemopoietic stem cells by two different techniques, both ofwhich allow for full reconstitution of long-tenn marrow culture hemopoiesis when combined with adherent cell-depleted bone marrow stem cells. 2 When these empty stromal layers were charged with FDC-Pl cells (that proliferate selectively to OM-CSF or IL-3) rather than stem cells, there was progressive growth of FDC-Pl cells, recognizable by their blast cell morphology, on normal + I +- WCB6Fl adherent cells (Figure 1). However, inoculation of FDC-Pl cells on adherent cell layers of the congenic littennate mouse, WCB6Fl-SIISld, was followed by very poor growth of the factor-dependent cell line or either extinction after a period of weeks. I Another very important difference in the outcome of interaction between FDC-Pl and normal + I + adherent cell layers vs. SIISld mouse adherent cell layers was the appearance of transformed growth factor-independent derivatives of FDC-Pl on + I +, but not SIISld, layers in approximately 50% of the experiments after 12 to 16 weeks. These transformed FDC-Pl derivative cell lines were also independent of the requirement for stromal cell support, and were tumorigenic in mice after single cell cloning. Studies in our laboratory to determine a cause for the transfonnation were not totally successful. We did observe the production of low quantities of a OM-CSF-like activity in factor-independent derivative cells capable of stimulating FDC-Pl proliferation, I but others have also observed such activity in cells that are still factor-dependent. 3,4 In addition, our detection of this activity was later (after the first few months) less successful, suggesting that it was an induced rather than constitutive phenomenon.

Original languageEnglish (US)
Title of host publicationGrowth Regulation and Carcinogenesis
Subtitle of host publicationVolume I
PublisherCRC Press
Number of pages12
ISBN (Electronic)9781351080774
ISBN (Print)0849359600, 9781315893228
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Derigs, H. G., Nahreini, T. S., Harrington, M., Burgess, G. S., English, D., Inhorn, L., Klingberg, D., Gabig, T. G., & Boswell, H. (2018). ras oncogene mediates paracrine interactions between leukemic progenitor cells and stromal elements. In Growth Regulation and Carcinogenesis: Volume I (pp. 267-278). CRC Press. https://doi.org/10.1201/9781351072328