Publicaciones científicas

Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

21-ene-2022 | Revista: 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.

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