The serum tryptase test: an emerging robust biomarker in clinical hematology

Abstract

During the past few years, a number of molecular markers have been developed in clinical hematology, most of them related to specific gene defects. However, there is also an unmet need to develop novel serologic parameters to improve diagnostics and prognostication in daily practice. Among these, the serum tryptase appears to be a most reliable biomarker of myeloid neoplasms. Elevated tryptase levels are found in subgroups of patients with mastocytosis, myelodysplastic syndrome, myeloproliferative neoplasm, acute myeloid leukemia, chronic myeloid leukemia and chronic eosinophilic leukemia. In these patients, the tryptase level is of diagnostic and/or prognostic significance. In mastocytosis, an elevated tryptase level is a minor criterion of systemic disease and in BCR-ABL1⁺ chronic myeloid leukemia, elevated tryptase at diagnosis correlates with treatment responses and overall survival. In patients with elevated tryptase, the enzyme also serves as follow-up parameter and can be employed to measure treatment-responses. In the current article, we review and update the perspectives of tryptase and provide recommendations for use of this conventional biomarker in daily practice.

Keywords::

• biomarker
• mastocytosis
• myeloid leukemias
• prognostication
• tryptase

Acknowledgements

This work has been carried out within the frame of two research projects funded by the Austrian Science Fund (FWF) – project SFB F4611 and SFB F4704-B20; however, no budget was required for this work.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• The serum tryptase test is a novel reliable biomarker for various myeloid neoplasms.

• The serum tryptase test can be used as screening parameter in patients with suspected myeloid neoplasms, including systemic mastocytosis and eosinophilic leukemias.

• In patients with mastocytosis, an elevated tryptase level is indicative of systemic involvement and helpful to grade and subclassify the disease.

• In BCR/ABL1⁺ CML, an elevated tryptase at diagnosis correlates with basophilia, treatment responses and with the overall survival and thus prognosis.

• In patients with CEL or MPN-eo, an elevated serum tryptase level correlated with the presence of a FIP1L1-PDGFRA fusion gene.

• In patients with AML, markedly elevated levels of serum tryptase are found in various groups of patients, including those in whom blast cells express PML-RARA, AML1-ETO or CBFB-MYH11.

• In AML patients who are in complete hematological remission after chemotherapy, a persistently elevated tryptase level is associated with an increased risk of relapse.

• In patients with markedly elevated tryptase at diagnosis, the serum tryptase level should be measured during follow-up; a further increase is often associated with disease progression; and in those who receive interventional treatment, the serum tryptase test can be employed to document and measure treatment responses.

Notes

^†In these patients baseline tryptase levels are compared to tryptase levels measured during an event. A clear elevation from baseline (20% plus total 2 ng/mL) is a criterion of MCAS [30].

AHNMD: Associated hematologic non-mast cell-lineage disease; CM: Cutaneous mastocytosis; FGFR: Fibroblast growth factor receptor; PDGFR: Platelet derived growth factor receptor.