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Novel genetic pathways causing tumor transformation discovered in a rare lymphoma subject

The study performed on a mouse model generated at the Cima University of Navarra could contribute to the early detection of B-cell lymphomas.

/Ibai Goicoechea, Bruno Paiva, José A. Martínez Climent, Sara Rodríguez y Ion Celay

12 | 04 | 2022

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

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

"We know that the cells of solid tumors and myeloid leukemias accumulate mutations years before the disease appears. However, in the case of B-cell lymphomas there was no contrasted information. Thanks to the information obtained from patient samples, in our laboratories at Cima we have generated a mousemodel with Waldenström macroglobulinemia to study genetic changes in early stages", explain Drs. José A. Martínez-Climent and Bruno Paiva, researchers in the Hemato-Oncology Program at Cima University of 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. That is, the origin of lymphoma occurs prior to cell mutation, so it is critical to delve into the knowledge of additional genetic changes in these cells," the researchers note. The results have been published in the scientific journal Science Advances.

The presence of these genetic pathways in normal B lymphocytes could be an 'ultra-early' marker of risk for developing lymphoma. "This information gives way to new strategies for early detection of this disease, as well as to further research into alternative methods to evaluate the efficacy of treatment in this subject of lymphomas, given the lack of specificity of the MYD88 mutation, since it is present in normal cells," conclude Drs. Paiva and Martinez-Climent.

Sara Rodríguez, Ion Celay, Ibai Goicoechea and Cristina Jiménez are the first authors of this collaborative work , which has been carried out at the framework of high school of research Sanitaria de Navarra (IdiSNA) and CIBER de Cáncer (CIBERONC).

reference letter bibliographic

- Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma.
Sci Adv. 2022 Jan 21;8(3):eabl4644. doi: 10.1126/sciadv.abl4644. Epub 2022 Jan 19.