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

Expert Opin Investig Drugs. 2018 Apr;27(4):377-387. doi: 10.1080/13543784.2018.1459562. Epub 2018 Apr 4.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation / physiology
  • Cell Survival / physiology
  • Drug Design
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / enzymology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction / drug effects
  • Syk Kinase / antagonists & inhibitors*
  • Syk Kinase / metabolism

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • SYK protein, human
  • Syk Kinase