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A Moving Target: Inactivating BTK Mutations as Drivers of Follicular Lymphoma

Jumana Afaghani1, Justin Taylor2,3

  • 1Division of Hematology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|February 13, 2021
PubMed

Insights

Bruton tyrosine kinase (BTK) inhibitors are effective for many B-cell lymphomas but not follicular lymphoma. Some follicular lymphomas may not need BTK, as shown by inactivating mutations.

Area of Science:

  • Oncology
  • Hematology
  • Molecular Biology

Background:

  • Bruton tyrosine kinase (BTK) inhibitors have revolutionized B-cell lymphoma treatment.
  • Lower efficacy of BTK inhibitors in follicular lymphoma (FL) remains unexplained.

Purpose of the Study:

  • To investigate the role of BTK in follicular lymphoma.
  • To understand the reasons behind the limited effectiveness of BTK inhibitors in FL.

Main Methods:

  • Analysis of BTK mutations in follicular lymphoma samples.
  • Functional studies to assess BTK dependency in FL cells.

Main Results:

  • Discovery of inactivating BTK mutations in a subset of follicular lymphomas.
  • Evidence suggests that some FLs do not depend on BTK signaling for survival or proliferation.

Conclusions:

  • Follicular lymphoma heterogeneity may explain variable responses to BTK inhibitors.
  • Targeting BTK may not be effective in FLs with inactivating BTK mutations.

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