Autostimulatory mechanisms in myeloid leukemogenesis.

WEHI-274 is a monocytic leukemia that arose in a BALB/c mouse infected with Abelson murine leukemia virus. A series of subclones were derived from early passages of this tumor. Three subsets of these leukemogenic subclones were identified. Two subsets demonstrated autostimulatory patterns of growth. This was due to the ectopic production of the T-cell lymphokine the panspecific hemopoietin IL-3 in one case and of the T-cell lymphokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in the other. The third type of subclone did not secrete any autostimulatory growth factor. In the subclone producing IL-3, one copy of IL-3 gene was rearranged and abnormal IL-3 RNA transcripts were present in the nucleus. Subclones producing GM-CSF also contained abnormal GM-CSF RNA transcripts, although no rearrangement of the GM-CSF gene was detected. All three sets of subclones shared a common rearrangement of one c-myb oncogene, suggesting that they share a common ancestor. These results suggest that initiation or progression of leukemogenic behavior in this abnormal clone occurred in three different ways, two of which involved autostimulation by the ectopic activation of T-cell lymphokine genes.