The effect of leukemic lymphoblasts on normal granulopoiesis

Acute lymphoblastic leukemia (ALL) in children is often characterized by defective granulopoiesis during initial and relapse stages of the disease, resulting in absolute neutropenia in vivo and in low or absent production of granulocyte-macrophage colonies in vitro. The purpose of this study was to determine if leukemic lymphoblasts from untreated ALL patients could inhibit normal granulopoiesis. Several concentrations of leukemic bone marrow cells from nine patients were mixed with either normal bone marrow cells or with autologous (HLA-identical) remission bone marrow cells, incubated for 1 hour, and co-cultured by the double layer agar technique. The cells were also cultured separately as controls. No statistically significant differences occurred between observed and expected colony counts in the majority of experiments. With three patients, slight inhibition occurred at some but not all leukemic cell concentrations tested; this inhibition was not correlated with the leukemic cell concentration. These results indicate that leukemic cells from untreated ALL patients do not significantly inhibit normal in vitro granulopoiesis at the committed stem cell level or at later levels of differentiation; therefore, such inhibition does not appear to be responsible for ALL-associated neutropenia.