Tumor necrosis factor, but not other hematopoietic growth factors, prolongs the survival of hairy cell leukemia cells.
In order to determine the growth factor requirements of hairy cell leukemia (HCL) cells, we studied the in vitro effects of tumor necrosis factor (TNF), interleukin (IL) 1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, B-cell growth factor (BCGF), GM-CSF, PHA-stimulated lymphocyte-conditioned media (CM), and 5637 bladder carcinoma CM on HCL cells obtained from spleens of patients with HCL. Mononuclear cells from a normal donor, obtained at post-traumatic splenectomy, served as a control. TNF prolonged the survival of HCL cells obtained from five different HCL patients when compared to cells cultured in control media alone, although cell proliferation could be demonstrated in only two of the five. HCL cells stained negative for the Epstein-Barr nuclear antigen (EBNA) both before and after 4 weeks in culture. BCGF, 5637 CM, and PHA-stimulated lymphocyte CM also prolonged the survival of HC25 and HC56 cells, although not to the same degree as TNF. Cells cultured in BCGF, however, stained positive for EBNA. None of the other recombinantly produced or purified cytokines prolonged the survival of the leukemic cells. With the exception of IL-2, none of the growth factors studied prolonged the survival of purified normal spleen (NS) cells over a 4-week period of time when compared to NS cells incubated in media alone. TNF prolonged the survival of HC25 cells in a dose-dependent manner, and a highly purified antibody to TNF abrogated the effects of TNF. HC25 cells incubated in the presence of control media alone did not constitutively produce TNF mRNA; however, incubation of the cells in the presence of TNF for 48 h induced the cells to express TNF message. We conclude that TNF is important in prolonging the survival of HCL cells, and thus may be important in the pathogenesis of this disease.
Schiller
J H
JH
William S. Middleton Veterans Administration Hospital, Madison, Wisconsin.
Bittner
G
G
Spriggs
D R
DR
D002470:Cell Survival; D003584:Cytological Techniques; D015322:Gene Rearrangement, B-Lymphocyte; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007943:Leukemia, Hairy Cell / Q000473:pathology*; D013154:Spleen / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016298:Hematopoietic Cell Growth Factors; D014409:Tumor Necrosis Factor-alpha