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bcr-abl-Induced cell lines can switch from mast cell to erythroid or
myeloid differentiation in vitro
AG Elefanty and S Cory
Walter and Eliza Hall Institute of Medical Research, Post Office Royal
Melbourne Hospital, Victoria, Australia.
The chimeric bcr-abl gene formed by the Philadelphia translocation is
thought to initiate chronic myeloid leukemia. Engraftment of mice with bone
marrow cells infected with a bcr-abl retrovirus has been shown to elicit
multiple hematopoietic disorders, including a clonal but nontransplantable
hyperproliferation of erythroid and/or mast cells. Culture of spleen and
bone marrow cells from such mice usually yielded mast cell lines, even when
erythroid disease dominated the primary animal. The mast cells, which
carried the same proviral insert as the primary disease, generally grew
slowly and were neither transplantable nor clonogenic in agar until they
had been cultured for several months. Unexpectedly, several bcr-abl-induced
lines switched in vitro from mast cell to megakaryocytic and/or erythroid
character, and one became myeloid. The dramatic phenotypic shifts seem
likely to involve changes occurring within progenitor cells maintaining the
clone, rather than mutation of mature mast cells. The variant lines
exhibited substantial spontaneous differentiation, despite being readily
transplantable and therefore fully transformed. The production of
hematopoietic growth factors by the mast cell lines and their phenotypic
variants may implicate an autocrine loop in their evolution. These novel
bcr-abl cell lines should aid in the study of genetic events in the
progression from chronic to acute leukemia and facilitate analysis of
hematopoietic lineage commitment.
Volume 79,
Issue 5,
pp. 1271-1281,
03/01/1992
Copyright © 1992 by The American Society of Hematology

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