6533b823fe1ef96bd127ed01
RESEARCH PRODUCT
Preneoplastic somatic mutations including MYD88(L265P) in lymphoplasmacytic lymphoma
Sara RodriguezJon CelayIbai GoicoecheaCristina JimenezCirino BottaMaria-josé Garcia-barchinoJuan José GarcésMarta LarrayozSusana SantosDiego AlignaniAmaia Vilas-zornozaCristina PerezSonia GarateSarai SarvideAitziber LopezHans-christian ReinhardtYolanda R. CarrascoIsidro Sanchez-garciaMaria-jose LarrayozMaria-jose CalasanzCarlos PanizoFelipe ProsperJose-maria Lamo-espinosaMarina MottaAlessandra TucciAntonio SaccoMassimo GentileSara DuarteHelena VitoriaCatarina GeraldesArtur PaivaNoemi PuigRamon Garcia-sanzAldo M. RoccaroGema FuerteJesus F. San MiguelJose-angel Martinez-climentBruno Paivasubject
Multidisciplinaryhemic and lymphatic diseasesLymphoplasmacytic lymphomalymphoplasmacytic lymphomaMYD88MutationsB cell lymphomasingle celldescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2022-01-21 |