Targeted Therapies for Lymphoma Patients Show Promise

Strategic Insights -

Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, have identified a mutation in the MYD88 gene that could lead to targeted therapies for certain lymphoma patients. This mutation, found to be one of the most frequent genetic abnormalities in diffuse large B cell lymphoma, can cause uncontrolled cellular signaling, leading to the survival of malignant cells. The study, which appeared in Nature on December 22, 2010, highlights the importance of genetic mutations in the development of cancers such as lymphoma. The researchers hope that their findings will lead to the development of new treatments for patients with the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma, which has a poor three-year survival outcome of 40 percent.

Key Takeaways:

  • A mutation in the MYD88 gene was found to be one of the most frequent genetic abnormalities in diffuse large B cell lymphoma, a form of non-Hodgkin's lymphoma.
  • The mutation leads to uncontrolled cellular signaling, causing the survival of malignant cells, and is more common in the ABC subtype of diffuse large B cell lymphoma.
  • The researchers identified a protein complex that includes IRAK1, IRAK4, and the mutant form of MYD88, which is required for lymphoma cell survival.
  • Pharmaceutical companies are developing IRAK4 inhibitors for use in inflammatory and autoimmune diseases, which may have direct therapeutic implications for lymphoma patients.
  • The study's findings may provide a method to identify patients with the ABC subtype of diffuse large B cell lymphoma whose tumors may depend on MYD88 signaling and who may benefit from therapies targeting IRAK4 alone or in combination with other agents.

Statistics:

  • 29 percent of ABC lymphoma samples had the same mutation in the MYD88 gene, which altered a single amino acid in the MYD88 protein.
  • The three-year survival outcome for patients with the ABC subtype of diffuse large B cell lymphoma is 40 percent.
  • The mutation was rare or absent in other lymphoma subtypes.

Sources:

  • Ngo VN, et al., Oncogenically active MYD88 mutations in human lymphoma, Nature, DOI: 10.1038/nature09671.
  • National Cancer Institute (NCI), part of the National Institutes of Health.
  • National Institutes of Health (NIH).
  • World Wide Web (www.cancer.gov and www.nih.gov).