biostudies-literatureSewastianik TNCI NIH HHS3360-3374https://www.ebi.ac.uk/biostudies/studies/S-EPMC6855113biostudies-literatureUnknown3(21)MYD88 L265P is the most common mutation in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and one of the most frequent in poor-prognosis subtypes of diffuse large B-cell lymphoma (DLBCL). Although inhibition of the mutated MYD88 pathway has an adverse impact on LPL/WM and DLBCL cell survival, its role in lymphoma initiation remains to be clarified. We show that in mice, human MYD88L265P promotes development of a non-clonal, low-grade B-cell lymphoproliferative disorder with several clinicopathologic features that resemble human LPL/WM, including expansion of lymphoplasmacytoid cells, increased serum immunoglobulin M (IgM) concentration, rouleaux formation, increased number of mast cells in the bone marrow, and proinflammatory signaling that progresses sporadically to cloBlood advancesHuman MYD88L265P is insufficient by itself to drive neoplastic transformation in mature mouse B cells.PMC6855113R01 CA196783Sewastianik TYang GJarolim PKofides APatel NAWright KTreon SPJiang MShanmugam VNag ATanton HHunter ZRGuerrera MLHuang YMunshi NCAdler KDalgarno ADennis PSCarrasco RDDemos MGPinkus GSfalseHuman MYD88L265P is insufficient by itself to drive neoplastic transformation in mature mouse B cells.MYD88 L265P is the most common mutation in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and one of the most frequent in poor-prognosis subtypes of diffuse large B-cell lymphoma (DLBCL). Although inhibition of the mutated MYD88 pathway has an adverse impact on LPL/WM and DLBCL cell survival, its role in lymphoma initiation remains to be clarified. We show that in mice, human MYD88L265P promotes development of a non-clonal, low-grade B-cell lymphoproliferative disorder with several clinicopathologic features that resemble human LPL/WM, including expansion of lymphoplasmacytoid cells, increased serum immunoglobulin M (IgM) concentration, rouleaux formation, increased number of mast cells in the bone marrow, and proinflammatory signaling that progresses sporadically to clo2019-01-01T00:00:00Z2019 Nov2026-05-04T11:20:37.094Z2021-02-19T23:44:30ZS-EPMC68551133169846410.1182/bloodadvances.2019000588