Development of a lethal mast cell disease in mice reconstituted with bone
marrow cells expressing the v-erbB oncogene
T von Ruden, S Kandels, T Radaszkiewicz, A Ullrich and EF Wagner
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
An animal model for malignant mastocytosis is described in mice
reconstituted with bone marrow cells expressing the v-erbB oncogene. The
lethal mast cell disease is characterized by massive infiltration of bone
marrow, spleen, and several other visceral organs by connective tissue mast
cells, which normally reside in the skin and the peritoneal cavity. As is
frequently found in malignant mastocytosis, the v-erbB- induced mast cell
disease was accompanied in some primary recipients by an acute myelogenous
leukemia (AML) that killed all secondary recipients regardless of whether
the AML was already evident in the primary host. The infiltrating mast
cells stained strongly positive with berberine sulfate, suggesting that
they were terminally differentiated and in vitro they showed only a weak
proliferative capacity. The leukemias were clonal but apparently of
different origin than the malignant mast cells, implying the transformation
of two independent cell populations. Leukemic cells expressed various
myeloid- specific markers as well as the B220 antigen, normally associated
with the B-cell lineage. However, the Ig heavy chain genes were still in
germ line configuration. In culture, these cells proliferated in the
absence of exogenous growth factors and had the capacity to differentiate
into mature myeloid cells. Preliminary experiments suggest that v-erbB may
use parts of a signal transduction pathway normally coupled to the c-kit
receptor. The v-erbB-induced malignant mast cell disease should provide a
useful animal model for elucidating the cause for malignant mastocytosis in
humans and to explore possible therapeutic strategies.
Volume 79,
Issue 12,
pp. 3145-3158,
06/15/1992
Copyright © 1992 by The American Society of Hematology
