Cell Growth & Differentiation, Vol 4, Issue 2 125-135, Copyright © 1993 by American Association of Cancer Research
Induction of pre-B lymphoid leukemia following reconstitution of lethally irradiated mice with v-erb-B virus-infected bone marrow progenitor cells
M Miller and G Symonds
Children's Medical Research Institute, Westmead, New South Wales, Australia.
We have previously shown that v-erb-B contained within a recombinant murine
retroviral vector is capable of transforming pre-B lymphocytes (M. Miller,
A. K. Kennewell, and G. Symonds, Leukemia, 6: 18-28, 1992) and early
erythroid precursor cells [blast-forming units (erythroid) (M. Miller, A.
Kennewell, Y. Takayama, A. Bruskin, J. M. Bishop, G. Johnson, and G.
Symonds, Oncogene, 5: 1125-1131, 1990)] in vitro. To determine the sites
and nature of v-erb-B-induced transformation in vivo, the hematopoietic
systems of lethally irradiated mice were repopulated with v-erb-B-infected
bone marrow. All mice became moribund within 4-12 weeks of reconstitution,
with a median onset of disease at 6 weeks. Histopathological and flow
cytometric evaluation of tissues from diseased mice, as well as
morphological and phenotypic analysis (cytochemical as well as molecular)
of the cell lines established from the mice, revealed that all but one of
the mice examined at postmortem had developed a pre-B lymphoid leukemia or
lymphoma. Abnormally high levels of mast cells in the spleen and bone
marrow of the remaining mouse indicated a mast cell disease. The
development of pre-B lymphoid malignancy in the majority of the
reconstituted mice indicates a marked predisposition of v-erb-B to
transform cells of the pre-B lymphoid lineage. The reconstitution of
lethally irradiated mice with v-erb-B virus-infected bone marrow provides a
model system for the analysis of events involved in the initiation and
maintenance of acute lymphoid leukemia.