Splenic tyrosine kinase (SYK) inhibitors and their possible use in acute myeloid leukemia

ABSTRACT

Introduction: Splenic tyrosine kinase (SYK) is a non-receptor tyrosine kinase. It is important for downstream signaling from several cell surface receptors, including Fc receptors, complement receptors and integrins. SYK can have either oncogenic or tumor suppressor activity in human malignancies. Recent studies suggest that SYK inhibition may have an antileukemic effect in human acute myeloid leukemia (AML).

Areas covered: Relevant publications were identified through literature searches in the PubMed database. We searched for (i) original articles describing the results from clinical studies of SYK inhibition; (ii) published articles describing the importance of SYK in human malignancies, especially AML.

Expert opinion: SYK is important for the downstream signaling from several cell surface receptors. There is also a crosstalk between SYK and signaling initiated through ligation of Toll like receptors, and SYK is thereby linked with the NFκB mediated transcriptional regulation. SYK activation will also influence PI3K-Akt-mTOR signaling. Several of these signaling events are important for survival and proliferation of primary human AML cells. In the present review we describe and discuss the role of SYK in human AML, and these data suggest that SYK inhibition is a possible therapeutic strategy in human AML.

KEYWORDS:

• Acute myeloid leukemia
• SYK
• SYK inhibitors
• signaling pathways

Article highlights

• Experimental studies show that SYK can be involved in several AML-driving intracellular circuits.

• Experimental studies suggest SYK inhibition as a possible therapeutic strategy in human AML

• SYK inhibitors seem to have an acceptable toxicity when used as monotherapy.

• SYK inhibition seems to have an increased hematological toxicity when used in patients with relapsed or resistant hematological malignancies.

• The toxicity of combination therapy has to be carefully evaluated in future clinical studies.

This box summarizes key points contained in the article.

Declaration of Interest

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.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The authors receive financial support for their scientific work from the University of Bergen, Norwegian Cancer Society, Helse-Vest and Eivind Møllbach Pedersens Foundation.