ABSTRACT
To investigate possible mechanisms of growth factor expression in acute myeloid leukemia, genes for granulocyte macrophage colony-stimulating factor (GM-CSF) were analyzed by Southern blots in 20 patients, for M-CSF in 13, for interleukin-6 (IL-6) in 14, for IL-6 receptor in 14 and for G-CSF in five patients. Only in one patient a complex rearrangement of the G-CSF gene with possible amplification was noted indicating rarity of direct alterations of growth factor genes in acute myelogenous leukemia (AML). Spontaneous m-RNA expression for GM-CSF was found in only one of 20 patients, and for IL-6 in eight of 11 patients. In vitro incubation of AML cells of eight patients with recombinant tumor necrosis factor for 24 hr revealed induction of GM-CSF m-RNA expression in three cases and GM-CSF protein expression in two of them. These data suggest that spontaneous GM-CSF production occurs rarely in AML and that monokines, such as tumor necrosis factor, may induce GM-CSF in AML cells. Therefore, interactions of AML cells with normal or malignant accessory cells may be important for autocrine stimulation in AML. Our data suggest that ectopic growth factor secretion is not the primary cause of generating AML but may contribute to progression of the disease. Alternatively, AML may represent a heterogenous group of leukemias with different etiology but similar phenotype.
Subject(s)
Colony-Stimulating Factors/genetics , Growth Substances/genetics , Interleukin-6/genetics , Leukemia, Myeloid, Acute/genetics , Blotting, Northern , Colony-Stimulating Factors/metabolism , Culture Media , Gene Expression , Granulocyte-Macrophage Colony-Stimulating Factor , Growth Substances/metabolism , Humans , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , RNA, Messenger/genetics , Time Factors , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Constitutive secretion of interleukin-6 (IL-6) has been proposed as a mechanism of transformation in multiple myeloma. We therefore studied 15 patients with this disease for rearrangements of the IL-6 and IL-6 receptor genes. Two patients with altered IL-6 genes were identified. Chromosome analysis revealed aberrations of chromosome 7, where the IL-6 gene resides, in only these two patients, but not in others without IL-6 rearrangements. In one of these patients, constitutive IL-6 m-RNA expression was observed. No alterations of IL-6 receptor genes were detected.
