| First Author | Rodriguez S | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 3 | Pages | eabl4644 |
| PubMed ID | 35044826 | Mgi Jnum | J:319632 |
| Mgi Id | MGI:6865088 | Doi | 10.1126/sciadv.abl4644 |
| Citation | Rodriguez S, et al. (2022) Preneoplastic somatic mutations including MYD88(L265P) in lymphoplasmacytic lymphoma. Sci Adv 8(3):eabl4644 |
| abstractText | 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. |
