Evaluation of biologic activity of tryptase secreted from blast cells in acute myeloid leukemia.
A number of autocrine and paracrine growth regulators are considered to be involved in the survival and proliferation of blast cells in acute myeloid leukemia (AML). We have recently shown that blast cells in a group of patients with AML produce and secrete the mitogenic enzyme tryptase. In the present study, we examined functional effects of tryptase in the context of AML. As assessed by 3H-thymidine uptake experiments, tryptase-containing serum from patients with AML as well as heparin-complexed recombinant tryptase were found to promote the proliferation of cultured bone marrow- and lung fibroblasts in a dose-dependent manner. A neutralizing antibody against human beta-tryptase was found to diminish these growth-stimulatory effects of serum-tryptase in all patients examined. Tryptase also induced the expression of mRNA for GM-CSF and SCF, two cytokines known to promote growth of AML cells, in cultured bone marrow fibroblasts. Neither recombinant tryptase nor tryptase-rich serum of AML patients, showed an effect on the growth of leukemic blast cells irrespective of the FAB category or expression of protease-activated receptor (PAR)-2, a putative molecular target of tryptase. Together, tryptase is secreted from AML blasts as a biologically active molecule that may exhibit paracrine rather than autocrine effects in AML.
Sonneck
Karoline
K
Department of Internal Medicine I, Division of Hematology & Hemostaseology - the Center of Excellence for Clinical and Experimental Oncology (CLEXO), Medical University of Vienna, Austria.
Florian
Stefan
S
Böhm
Alexandra
A
Krauth
Maria-Theresa
MT
Kondo
Rudin
R
Hauswirth
Alexander W
AW
Gleixner
Karoline V
KV
Aichberger
Karl J
KJ
Derdak
Sophia
S
Pickl
Winfried F
WF
Sperr
Wolfgang R
WR
Schwartz
Lawrence B
LB
Valent
Peter
P
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001752:Blast Crisis / Q000201:enzymology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019899:Paracrine Communication; D012697:Serine Endopeptidases / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D014316:Tritium / Q000493:pharmacokinetics; D053802:Tryptases
D016207:Cytokines; D014316:Tritium; D012697:Serine Endopeptidases; D053802:Tryptases