Bone marrow stromal deficiency in acute myeloid leukemia in mice

Abstract

A study of bone marrow stroma in acute myeloid leukemia (AML) in mice was carried out. AML was induced in C57B1 mice by i.v. inoculation of the C1498 cell line. There was a direct correlation between the marrow leukemic load and the degree of marrow stromal deficiency. This was expressed by reduced in vitro fibroblastoid colony formation. In co-cultures of normal mouse bone marrow and leukemic cells, and also in cultures of normal marrow with added conditioned medium (CM) of leukemic cells, marked inhibition of fibroblast-colony-forming units (CFU-F) from normal marrow was observed. In additional experiments, leukemic mice were treated with two consecutive injections of cytosine arabinoside (Ara-C) (2 × 200mg/kg) and sacrificed 48 h later. Bone marrow samples of treated animals formed in vitro an increased number of fibroblastoid colonies despite relatively high levels of marrow leukemia. It is concluded that: (a) there is a direct correlation between the incidence of marrow leukemic cells and the degree of stromal deficiency; (b) leukemic cells produce in vitro—and probably in vivo CFU-F inhibitory factors and (c) administration of restricted doses of cytosine arabinoside to leukemic mice reduces the marrow leukemic cell content to some extent and increases the capacity of CFU-F to form fibroblastoid colonies in vitro.