Novel approaches to targeting MYD88 in Waldenström macroglobulinemia

Expert Rev Hematol. 2017 Aug;10(8):739-744. doi: 10.1080/17474086.2017.1343661. Epub 2017 Jun 28.


Waldenström macroglobulinemia (WM) is an incurable lymphoma characterized by the accumulation of IgM-producing lymphoplasmacytic cells in the bone marrow and other organs. Although WM patients can experience prolonged remissions, the disease invariably recurs advocating for the need of novel treatments in order to achieve higher response and survival rates. The discovery of a recurrent mutation in the MYD88 gene and an increased understanding behind the biology of MYD88 signaling have provided the opportunity to developing novel agents targeting the MYD88 pathway. Areas covered: The present review focuses on potential therapies that could change the landscape of treatment of patients with WM, specifically focusing on inhibitors of the Bruton tyrosine kinase (BTK), phosphatidylinositol-3 kinase, hematopoietic cell kinase, interleukin-1 receptor associated kinase and MYD88 assembly. Expert commentary: Novel agents such as the BTK inhibitor ibrutinib has shown to be safe and highly effective in the treatment of WM. Ibrutinib has been approved in Europe and the United States for its use in patients with symptomatic WM. Prospective studies are ongoing and/or planned to study many other novel agents alone and in combination with aims at improving response, survival and quality of life in patients with WM.

Keywords: BCL2; BTK; CD38; CXCR4; MYD88; PI3K; Waldenström macroglobulinemia.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / antagonists & inhibitors
  • Interleukin-1 Receptor-Associated Kinases / genetics
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Molecular Targeted Therapy*
  • Mutation
  • Myeloid Differentiation Factor 88 / antagonists & inhibitors*
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Binding
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Multimerization / drug effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins c-hck / antagonists & inhibitors
  • Proto-Oncogene Proteins c-hck / genetics
  • Proto-Oncogene Proteins c-hck / metabolism
  • Signal Transduction / drug effects
  • Toll-Like Receptors / antagonists & inhibitors
  • Toll-Like Receptors / metabolism
  • Waldenstrom Macroglobulinemia / drug therapy*
  • Waldenstrom Macroglobulinemia / genetics
  • Waldenstrom Macroglobulinemia / metabolism*


  • Myeloid Differentiation Factor 88
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Toll-Like Receptors
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Proto-Oncogene Proteins c-hck
  • Interleukin-1 Receptor-Associated Kinases