Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia

Abstract

α- and β-tryptase genes encode serine proteases that are abundantly expressed by mast cells. Under physiologic conditions other myeloid cells are virtually tryptase negative. However, tryptases are also expressed in several myeloid leukemia cell lines. In this study, serum total tryptase levels were determined in 150 patients with acute leukemias (de novo acute myeloid leukemia [AML], n = 108; secondary AML, n = 25; acute lymphoid leukemia [ALL], n = 17) by fluoroenzyme immunoassay. In healthy subjects (n = 30), tryptase levels ranged between 2.0 and 12.6 ng/mL. Elevated tryptase levels (> 15) were detected in 42 (39%) of 108 patients with de novo AML and in 11 (44%) of 25 patients with secondary AML. No elevated tryptase levels were found in patients with ALL. In de novo AML, elevated tryptase levels were frequently detected in patients with French-American-British classification M0 (6 of 9), M2 (9 of 14), M3 (4 of 6), and M4eo (7 of 7), and less frequently in M1 (7 of 20), M4 (6 of 26), M5 (2 of 18), M6 (0 of 5), or M7 (1 of 3). The highest tryptase levels were found in M4eo. Immunohistochemical staining of bone marrow sections with anti-tryptase antibody as well as immunoelectron microscopy revealed tryptase expression in the cytoplasm of myeloblasts. As assessed by Northern blotting and reverse transcriptase–polymerase chain reaction, AML cells expressed α-tryptase messenger RNA (mRNA) but little or no β-tryptase mRNA. In AML patients with elevated serum tryptase before chemotherapy, who entered complete remission, tryptase levels returned to normal or near normal values. Blast cell persistence or regrowth was associated with a persistently elevated level or recurrent increase of tryptase. Together, tryptase is expressed in myeloblasts in a group of AML and may serve as a useful disease-related marker.