High frequency of myelomonocytic tumors in aging E mu L-myc transgenic mice.
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.
Möröy
T
T
Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Fisher
P E
PE
Lee
G
G
Achacoso
P
P
Wiener
F
F
Alt
F W
FW
D000375:Aging; D000818:Animals; D015152:Blotting, Northern; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015870:Gene Expression; D016259:Genes, myc / Q000235:genetics*; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics* / Q000473:pathology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D008637:Mesenchymoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007143:Immunoglobulin Heavy Chains; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor