Spanish researchers discover new genetic pathways causing tumor transformation in a rare type of lymphoma

Waldenström's macroglobulinemia is a rare B-cell lymphoma. It represents 2% of hematological malignancies, although it shares the same gene (MYD88) mutation with other types of lymphoma.

Researchers at Cima Universidad de Navarra have discovered new genetic pathways that cause the mutation of healthy cells and the tumor transformation in this type of lymphoma. This finding could contribute to the early detection of this and other B-cell lymphomas with MYD88 mutations.

"We know that cells from solid tumors and myeloid leukemias accumulate mutations years before the disease appears. However, there was no proven information on the case of B-cell lymphomas. Thanks to the information obtained from patient samples we have generated in our laboratories at Cima, a mouse model of Waldenström's macroglobulinemia. We used this model to study genetic changes in early stages", explained Drs José A. Martínez-Climent and Bruno Paiva. Both are researchers in the Hemato-Oncology Program at Cima Universidad de Navarra and directors of the collaborative work.

Using sequencing techniques, the scientists observed a similar accumulation of random mutations in healthy B cells. "We discovered genetic and transcriptional pathways that drive malignant transformation. The origin of lymphoma occurs before cell mutation, so it is critical to deepening our understanding of additional genetic changes in these cells", the researchers noted. The results have been published in the scientific journal Science Advances.

These genetic pathways in normal B lymphocytes could be an 'ultra-early' marker of risk for developing lymphoma. "Given the lack of specificity of the MYD88 mutation, since it is present in normal cells, this information opens the way to new strategies for early detection of this disease. It also favors further research into alternative methods to evaluate treatment efficacy in this type of lymphoma," Drs. Paiva and Martínez-Climent concluded.

Sara Rodriguez, Ion Celay, Ibai Goicoechea, and Cristina Jimenez are the first authors of this collaborative work. It was realized within the framework of the Institute for Health Research of Navarra (IdiSNA) and CIBER Cancer (CIBERONC). It also was supported by the Roberto Arnall Planelles Foundation and the Spanish Association Against Cancer, among other funding sources.

Photo caption: From left to right: Ibai Goicoechea, Bruno Paiva, Jose A. Martinez Climent, Sara Rodriguez, and Ion Celay.