Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene

Abstract

Interleukin-3 (multi-CSF) is a multilineage haematopoietic growth regulator that initiates the proliferation and differentiation of multipotential stem cells. Complementary DNA clones encoding interleukin-3 (IL-3) have recently been isolated and the structure of the IL-3 gene determined. IL-3 is produced by T lymphocytes or T lymphomas only after stimulation with antigens, mitogens or chemical activators such as phorbol esters. The myelomonocytic leukaemia line WEHI-3B also produces IL-3 but its production is constitutive and the WEHI-3B cells do not appear to produce significant levels of any of the other lymphokines normally secreted by T lymphocytes after stimulation. It has been proposed that the genetic change leading to the constitutive expression of IL-3 may have been a key event in the development of this leukaemia. We report here that the constitutive synthesis of IL-3 by the WEHI-3B cell line is due to the insertion of an endogenous retrovirus-like element close to the 5' end of the gene. The insertion, an intracisternal A particle (IAP) genome, is positioned with its 5' long terminal repeat (LTR) close to the promoter region of the IL-3 gene, resulting in constitutive synthesis of IL-3.