B-cell enforced expression of the mouse ortholog of MYD88L265P is responsible for Waldenstrom-like B-cell lymphoma.

Here, we created a conditional transgenic mouse model with insertion of a sequence coding for both MYD88L252P and the Yellow Fluorescent Protein (YFP) into the rosa26-locus. B-cell specific induction of the transgene constantly led to spleen enlargement with expansion of YFP positive B-cells in 8-12 month-old mice, with a moderate B-cell proliferation increase. Being clonal or oligoclonal, these B-cells exhibited a marked morphological and immunophenotypic lymphoplasmocytic aspect with a plasma cell transcriptomic signature and a serum immunoglobulin M peak. Therefore, continuous activation of MYD88 in mice can lead on its own to a lymphoma close to Waldenstrom Macroglobulinemia.\n\nKey pointB-cell specific enforced expression of MYD88L252P leads to a clonal indolent lymphoplasmocytic B-cell lymphoma with a serum IgM peak.