Journal of Experimental Medicine, Vol 175, 313-322, Copyright © 1992 by Rockefeller University Press
High frequency of myelomonocytic tumors in aging E mu L-myc transgenic mice
T Moroy, PE Fisher, G Lee, P Achacoso, F Wiener and FW Alt
Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Transgenic mice that contain constructs of the L-myc gene under the
transcriptional control of the immunoglobulin heavy chain enhancer (E mu)
develop thymic hyperplasia and are predisposed to T cell lymphomas. Here we
describe a second form of malignancy that occurs in aging E mu L-myc
transgenic mice. The mean latency period for the development of this
malignancy is longer compared with the E mu L-myc T cell lymphomas but the
overall incidence is increased threefold. The histopathological morphology
is that of a highly malignant mesenchymal neoplasm that closely resembles
human fibrous histiocytoma. The tumor cells were classified as
myelomonocytic on the basis of several lineage-specific markers and the
lack of rearrangements of the immunoglobulin heavy chain and the T cell
receptor beta loci. Cultured tumor cells produce macrophage
colony-stimulating factor (M-CSF) protein and express the M- CSF receptor,
suggesting the involvement of an autocrine loop in this malignancy. Similar
to the E mu L-myc T cell lymphomas, these tumors show high-level transgene
expression but no detectable levels of endogenous c-myc mRNA, directly
implicating the deregulated expression of L-myc in the generation of this
malignancy. E mu L-myc myelomonocytic tumors show consistent trisomy of
chromosome 16, implicating this as a secondary event in the development of
this tumor. In the light of recent findings that L-myc is expressed in
human myeloid leukemias and in several human myeloid tumor cell lines, the
results described here might implicate L-myc in the development of
naturally occurring myeloid neoplasias.
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