Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia
Open accessAbstract
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.
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An elevated basal serum tryptase level by itself is neither an indication for MCA or MCAS nor an a priori risk factor for MCA or MCAS.
“an elevated basal serum tryptase level per se is neither an indication for MCA or MCAS nor is it an ‘a priori’ risk factor for the occurrence of MCA or MCAS.”
From Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome (2019) · cites this paper as [68]
The Discussion (p. 7) reports that elevated serum tryptase can come from AML blasts rather than mast cells, supporting the point that an elevated level alone does not establish mast-cell activation. The paper does not assess whether basal tryptase is a risk factor for MCA or MCAS. (LLM, conf=0.84)
Experimental — accuracy not yet measuredElevated basal tryptase is found in mastocytosis, hereditary alpha-tryptasemia where anaphylaxis risk may be increased, and myeloid non-MC-lineage neoplasms.
“an elevated basal tryptase level is not only found in patients with mastocytosis or hereditary alpha-tryptasemia (where the risk for anaphylaxis may be increased) but also in patients with myeloid non-MC-lineage neoplasms (Supplemental Table S1) (68-71).”
From Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome (2019) · cites this paper as [68]
The Discussion (p. 7) identifies tryptase as a marker of mastocytosis, and the Results (p. 3) report elevated serum tryptase in subsets of patients with acute myeloid leukemia, a non-mast-cell-lineage neoplasm. The paper does not address hereditary alpha-tryptasemia or its possible association with anaphylaxis risk. (LLM, conf=0.88)
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References 65 · Cited by 149
- Authors
- Sperr, W. R., Jordan, J.-H., Baghestanian, M., Kiener, H.-P., Samorapoompichit, P., Semper, H., Hauswirth, A., Schernthaner, G.-H., Chott, A., Natter, S., Kraft, D., Valenta, R., Schwartz, L. B., Geissler, K., Lechner, K., & Valent, P.
- Affiliations
- University of Vienna (AT)
- Corresponding author
- Sperr, Wolfgang R.
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2001-10-01
- Volume
- 98
- Issue
- 7
- Pages
- 2200-2209
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2164842318
- Cited by
- 149
- References
- 65
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 9 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 10 · 2013: 9 · 2012: 7
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI20487)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR45441, R01AR045441)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- serum tryptase, acute myeloid leukemia, myeloblasts, beta-tryptase, tryptase, acute lymphoblastic leukemia, secondary acute myeloid leukemia, disease markers, complete remission
- MeSH terms
- Acute Disease, Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Bone Marrow Cells, Female, Humans, Immunohistochemistry, Leukemia, Myeloid, Male, Mast Cells, Middle Aged, Monocytes, Remission Induction, RNA, Messenger, Serine Endopeptidases, Biomarkers, Microscopy, Immunoelectron, Myeloid Cells, Tryptases
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