Growth of human AML cell lines on bone marrow feeder layers is supported by cellular interactions rather than growth...

Leukemia is characterized by an excessive and anomalous cell growth which does not permit the cells to mature normally. Many cellular oncogenes have been shown to regulate such behavior and the participation of various growth factors has been implicated in the same process. The etiology of the proliferative stimulus is examined here and it is found that the cause of accelerated growth is mainly due to cellular interactions via surface contact. In order to reproduce the in vivo situation, that is the genesis and maturation of cells in the bone marrow compartment, acute myelogenous leukemia (AML) cells in the form of cell lines as well as primary APML cells were seeded on top of normal bone marrow feeder layers used as the supporting cellular surface. First, it is shown that direct contact between the two different populations results in increased proliferation of the seeded population as feeders, inactivated by irradiation, still stimulate cellular and do not promote differentiation. Second, it is demonstrated that there is no granulocyte-monocyte colony-stimulating factor (GM-CSF), CSF-1, interleukin-3 (IL-3) and possibly stem cell factor (SCF) production by the marrow cells during the contact. Third, when cell-to-cell contact is hindered by mechanically separating the cellular surfaces, allowing, however, the free transport of possibly produced growth factors (GF), the proliferative rate is reduced. Thus, the results demonstrate that cell contact and not growth factor production is responsible for the increased growth rate of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)