Preneoplastic somatic mutations including MYD88(L265P) in lymphoplasmacytic lymphoma
| Autor: | Sara Rodriguez, Jon Celay, Ibai Goicoechea, Cristina Jimenez, Cirino Botta, Maria-José Garcia-Barchino, Juan-Jose Garces, Marta Larrayoz, Susana Santos, Diego Alignani, Amaia Vilas-Zornoza, Cristina Perez, Sonia Garate, Sarai Sarvide, Aitziber Lopez, Hans-Christian Reinhardt, Yolanda R. Carrasco, Isidro Sanchez-Garcia, Maria-Jose Larrayoz, Maria-Jose Calasanz, Carlos Panizo, Felipe Prosper, Jose-Maria Lamo-Espinosa, Marina Motta, Alessandra Tucci, Antonio Sacco, Massimo Gentile, Sara Duarte, Helena Vitoria, Catarina Geraldes, Artur Paiva, Noemi Puig, Ramon Garcia-Sanz, Aldo M. Roccaro, Gema Fuerte, Jesus F. San Miguel, Jose-Angel Martinez-Climent, Bruno Paiva |
|---|---|
| Přispěvatelé: | Rodriguez, Sara, Celay, Jon, Goicoechea, Ibai, Jimenez, Cristina, Botta, Cirino, Garcia-Barchino, Maria-José, Garces, Juan-Jose, Larrayoz, Marta, Santos, Susana, Alignani, Diego, Vilas-Zornoza, Amaia, Perez, Cristina, Garate, Sonia, Sarvide, Sarai, Lopez, Aitziber, Reinhardt, Hans-Christian, Carrasco, Yolanda R, Sanchez-Garcia, Isidro, Larrayoz, Maria-Jose, Calasanz, Maria-Jose, Panizo, Carlo, Prosper, Felipe, Lamo-Espinosa, Jose-Maria, Motta, Marina, Tucci, Alessandra, Sacco, Antonio, Gentile, Massimo, Duarte, Sara, Vitoria, Helena, Geraldes, Catarina, Paiva, Artur, Puig, Noemi, Garcia-Sanz, Ramon, Roccaro, Aldo M, Fuerte, Gema, San Miguel, Jesus F, Martinez-Climent, Jose-Angel, Paiva, Bruno |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Dadun. Depósito Académico Digital de la Universidad de Navarra Consejo Superior de Investigaciones Científicas (CSIC) |
| Popis: | Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88 . We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88 L265P in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88 L265P is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|