| Title: |
Preneoplastic somatic mutations including MYD88(L265P) in lymphoplasmacytic lymphoma |
| Authors: |
Rodríguez-Díaz, S. (Saray); Celay, J. (Jon); Goicoechea, I. (Ibai); Jiménez, C. (Cristina); Botta, C. (Cirino); García-Barchino, M.J. (María José); Garcés-Latre, J.J. (Juan José); Larrayoz, M. (Marta); Santos, S. (S.); Alignani, D. (Diego); Vilas, A. (Amaia); Perez, C. (Cristina); Gárate-Luzuriaga, S. (Sonia); Sarvide, S. (Sarai); López-de-Arancibia, A. (Aitziber); Reinhardt, H.C. (Hans Christian); Carrasco, Y.R. (Yolanda R.); Sanchez-Garcia, I. (Isidro); Larrayoz, M.J. (María J.); Calasanz-Abinzano, M.J. (Maria Jose); Panizo, C. (Carlos); Prosper-Cardoso, F. (Felipe); Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María); Motta, M. (Marina); Tucci, A. (Alessandra); Sacco, A. (Antonio); Gentile, M. (Massimo); Duarte, S. (Sara); Vitoria, H. (Helena); Geraldes, C. (Catarina); Paiva, A. (Artur); Puig, N. (Noemí); García-Sanz, R. (Ramón); Roccaro, A.M. (Aldo M.); Fuerte, G. (Gema); San-Miguel, J.F. (Jesús F.); Martinez-Climent, J.A. (José Ángel); Paiva, B. (Bruno) |
| Publication Year: |
2022 |
| Collection: |
dadun - Depósito Académico Digital Universidad de Navarra |
| Subject Terms: |
Lymphoplasmacytic lymphoma; Mutations; MYD88 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
info:eu-repo/grantAgreement/EC/H2020/680200/EU; https://hdl.handle.net/10171/63093 |
| Availability: |
https://hdl.handle.net/10171/63093 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.F3C6DF2 |
| Database: |
BASE |