Different types of human leukemias express the message for TNF-alpha and interleukin-10.
Leukemic cells proliferate under the influence of cytokines. In particular, the colony-stimulating factors stimulate the growth and proliferation of myeloid leukemia cells. Under normal conditions, tumor necrosis factor-alpha (TNF-alpha) is produced by activated monocytes, whereas interleukin- 10 (IL-10) is produced by several cell types like monocytes and lymphocytes. The autocrine production of cytokines by leukemic cells may have a pathogenic role in the progression of leukemia or may be an epiphenomenon. In this study, we investigated the expression of TNF-alpha and IL-10 in human leukemic cells by RT-PCR and by a cytoplasmic protein assay. Most cases of acute myelogenous leukemia (AML) (7/8 cases) and all cases of acute lymphoblastic leukemia (ALL) (n = 2), chronic myelogenous leukemia (CML) (n = 5), both in chronic phase and during blast crisis, expressed the mRNA for TNF-alpha and IL-10. A patient whose blasts were positive for IL-10 and negative for TNF-alpha, had high circulating levels of IL-10 and failed to respond to donor lymphocyte infusions. Using a cytoplasmic protein assay, generally low levels of cytoplasmic TNF-alpha and IL-10 were found which increased in case of TNF-alpha following stimulation with lipopolysaccharide. Taken together, our data show that most leukemic cells express the mRNA for a proinflammatory cytokine (TNF-alpha) and an immunosuppressive cytokine (IL-10). More work is necessary to determine under which conditions these cytokines actually paralyze the immune system and thereby permit the progression of leukemia.
Schulz
U
U
Medizinische Klinik III der LMU, Klinikum Grosshadern, München, Germany.
Munker
R
R
Ertl
B
B
Holler
E
E
Kolb
H J
HJ
D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D007938:Leukemia / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000097:blood; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10