In conclusion, in this small case series we showed that MYD88L265P mutation analysis could serve as a useful adjunct in distinguishing benign from lymphomatous PE in patients with LPL.
The diagnosis of Waldenström Macroglobulinaemia (WM)/lymphoplasmacytic lymphoma (LPL) remains one of exclusion because other B-cell lymphoproliferative disorders (B-LPD), such as marginal zone lymphoma (MZL), can fulfil similar criteria, including MYD88L265P mutation.
The diagnosis of WM is established by the presence of lymphoplasmacytic lymphoma in the bone marrow or other organs, a monoclonal IgM paraproteinemia and the recurrent MYD88L265P somatic mutation.
Characteristics of Waldenström Macroglobulinemia in Korean Patients According to Mutational Status of MYD88 and CXCR4: Analysis Using Ultra-Deep Sequencing.
The mutation profile of MYD88 genes was evaluated by Sanger sequencing in a cohort of 97 patients [DLBCL (N=55), non-DLBCL lymphomas (N=30), reactive lymphadenopathy (N=10), and 2 cases of lymphoplasmacytic lymphoma (positive control)].
<i>Results</i>: MYD88L265P mutations were detected in 22 of 29 samples from 14 patients with diffuse large B-cell lymphomas and one patient with lymphoplasmacytoid lymphoma.
Detection of MYD88L265P mutation by next-generation deep sequencing in peripheral blood mononuclear cells of Waldenström's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance.
A risk-stratification model based on the initial concentration of the serum monoclonal protein and MYD88 mutation status identifies a subset of patients with IgM monoclonal gammopathy of undetermined significance at high risk of progression to Waldenström macroglobulinaemia or other lymphoproliferative disorders.
The simultaneous presentation of Waldenström's macroglobulinemia and MYD88 mutation with multiple myeloma in the same patient is very rare and only a few cases have been reported in the literature.
MyD88-loaded EVs were detected in the bone marrow aspirates of WM patients thus establishing the physiological role of EVs for MyD88<sup>L265P</sup> transmission and shaping of the proinflammatory microenvironment.
Owing to low prevalence of the wild-type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10-fold increased risk of mortality in this subgroup compared to patients with MYD88<sup>L265P</sup> mutation.
Few cancers such as WM have a single amino acid substitution in one gene like MYD88L265P that occurs in ∼90% of cases, making WM paradigmatic for study of a single causative mutation in oncogenesis.
To clarify if cytokine release by ibrutinib-treated BTK<sup>Cys481Ser</sup> cells could protect BTK<sup>WT</sup> MYD88-mutated malignant cells, we used a Transwell coculture system and showed that nontransduced BTK<sup>WT</sup> MYD88-mutated WM or ABC DLBCL cells were rescued from ibrutinib-induced killing when cocultured with BTK<sup>Cys481Ser</sup> but not their BTK<sup>WT</sup>-expressing counterparts.
Review of our genetic data on diffuse large B cell lymphoma (DLBCL) and Waldenstrom macroglobulinemia (WM), found that a large percentage of DLBCL and WM cases that have a MYD88 mutation also harbor a TNFAIP3 loss, 55% DLBCL and 28% of WM, respectively.
<b>Purpose:</b> Everolimus inhibits mTOR, a component of PI3K/AKT prosurvival signaling triggered by MYD88 and CXCR4-activating mutations in Waldenstrom macroglobulinemia.<b>Experimental design:</b> We evaluated everolimus in a prospective, multicenter study of 33 symptomatic, previously untreated Waldenstrom macroglobulinemia patients.
We identified the MYD88L265P somatic variant in cases with WM (39/42), MGUS (8/18), NHL (14/41, including 4/13 diffuse large B cell lymphoma (DLBCL), 1/8 mucosa-associated lymphoid tissue, 3/6 splenic marginal zone lymphoma (SMZL), 1/4 chronic lymphocytic leukemia, 2/3 nodal marginal zone lymphoma (NMZL), 1/2 mantle cell lymphoma, 1 Burkitt lymphoma, and 1 B cell NHL that could not be classified), primary AL (2/2), and IgM-PN (1/1).