GROWTH OF HUMAN AML CELL-LINES ON BONE-MARROW FEEDER LAYERS IS SUPPORTED BY CELLULAR INTERACTIONS RATHER THAN GROWTH-FACTOR PRODUCTION

Leukemia is characterized by an excessive and anomalous cell growth wh ich does not permit the cells to mature normally. Many cellular oncoge nes have been shown to regulate such behavior and the participation of various growth factors has been implicated in the same process. The e tiology of the proliferative stimulus is examined here and it is found that the cause of accelerated growth is mainly due to cellular intera ctions via surface contact. In order to reproduce the in vivo situatio n, that is the genesis and maturation of cells in the bone marrow comp artment, acute myelogenous leukemia (AML) cells in the form of cell li nes as well as primary APML cells were seeded on top of normal bone ma rrow feeder layers used as the supporting cellular surface. First, it is shown that direct contact between the two different populations res ults in increased proliferation of the seeded population as feeders, i nactivated by irradiation, still stimulate cellular and do not promote differentiation. Second, it is demonstrated that there is no granuloc yte-monocyte colony-stimulating factor (GM-CSF), CSF-1, interleukin-3 (IL-3) and possibly stem cell factor (SCF) production by the marrow ce lls during the contact. Third, when cell-to-cell contact is hindered b y mechanically separating the cellular surfaces, allowing, however, th e free transport of possibly produced growth factors (GF), the prolife rative mte is reduced. Thus, the results demonstrate that cell contact and not growth factor production is responsible for the increased gro wth rate of these cells. However, this kind of proliferation can be re versed by masking certain antigenic determinants of the feeder populat ion by specific monoclonal antibodies directed against class I, II and endothelial epitopes. This finding may be of importance for the contr ol of the disease in future trials.