Scientific publications

Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

Jan 21, 2022 | Magazine: Science Advances

Sara Rodriguez  1 , Jon Celay  1 , Ibai Goicoechea  1 , Cristina Jimenez  2 , Cirino Botta  3 , Maria-José Garcia-Barchino  1 , Juan-Jose Garces  1 , Marta Larrayoz  1 , Susana Santos  4 , Diego Alignani  1 , Amaia Vilas-Zornoza  1 , Cristina Perez  1 , Sonia Garate  1 , Sarai Sarvide  1 , Aitziber Lopez  1 , Hans-Christian Reinhardt  5 , Yolanda R Carrasco  6 , Isidro Sanchez-Garcia  7 , Maria-Jose Larrayoz  1 , Maria-Jose Calasanz  1 , Carlos Panizo  1 , Felipe Prosper  1 , Jose-Maria Lamo-Espinosa  1 , Marina Motta  8 , Alessandra Tucci  8 , Antonio Sacco  9 , Massimo Gentile  10 , Sara Duarte  4 , Helena Vitoria  11 , Catarina Geraldes  4 , Artur Paiva  4 , Noemi Puig  2 , Ramon Garcia-Sanz  2 , Aldo M Roccaro  9 , Gema Fuerte  12 , Jesus F San Miguel  1 , Jose-Angel Martinez-Climent  1 , Bruno Paiva  1


Abstract

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 MYD88L265P 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, MYD88L265P is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas.

CITATION  Sci Adv. 2022 Jan 21;8(3):eabl4644.  doi:10.1126/sciadv.abl4644.  Epub 2022 Jan 19

Our authors

Graduada adscrita al proyecto del Grupo de Mieloma Múltiple del Cima Universidad de Navarra
Sara del Mar Rodríguez Escobar
Director | Principal Investigator Cytometry Platform
Senior Researcher | Principal Investigator Multiple Myeloma Research Group
Jon Celay Leoz
Investigador postdoctoral del Grupo de Mieloma múltiple del Cima Universidad de Navarra
Ibai Goicoechea Oroz
María José García Barchino
Graduado adscrito al proyecto del Grupo de Mieloma Múltiple del Cima Universidad de Navarra
Juan José Garcés Latre
Marta Larráyoz Ilundáin
Diego Alignani
Senior Research Technician Cytometry Platform
Investigadora predoctoral del Grupo de Mieloma Múltiple del Cima Universidad de Navarra
Cristina Pérez Ruiz
Silueta investigadora
Sonia Gárate Luzuriaga
Laboratory technician Cytometry Platform
Sarai Sarvide Plano
Laboratory technician Multiple Myeloma Research Group
Silueta investigadora
Aitziber López López
Laboratory technician Cytometry Platform
Senior Researcher | Principal Investigator Multiple Myeloma Research Group