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MYD88 Mutation, Other Distinguishing Characteristics May Help Identify WM

John Otrompke

MYD88 mutation and increased IgM peak levels help to distinguish Waldenström macroglobulinemia (WM) from other indolent B-cell malignancies. In the study, the MYD88 mutation was found in almost all (93%, n = 25/27) WM cases.

“We evidenced a CD138 expression continuum between monotypic B-cells and (plasma cells) PCs. This pattern remained absent in control samples and was significantly associated with higher IgM peaks (P = 6.10-5) and MYD88 mutations (P = 10-3) in both WM and (IgM monoclonal gammopathy of undetermined significance) MGUS cases,” wrote lead author Mylene Gayet, Biological Hematology Department, University Hospital Dupuytren, Limoges, France, and co-authors.

The researchers performed routine flow cytometry (FCM) analysis on both B-cells and PCs from of 77 patients with IgM peak. MYD88 and CXCR4 mutations were studied using an allele-specific polymerase chain reaction (PCR) and by high throughput sequencing.

Of the cohort, 27 (35%) were classified as WM, 46 (58%) were MGUS, and 4 (5%) were B-cell non-Hodgkin lymphoma (B-NHL). MYD88 mutation was found in 25 of 27 (93%) WM and in 29 of 46 (63%) MGUS. Monotypic CD138pos/CD38pos PCs were detected in 23 of 27 (85%) WM and 25 of 46 (54%)MGUS.

“Highlighting the ongoing PC differentiation of WM tumor B-cells by FCM, we evidenced a CD138 expression continuum between monotypic B-cells and PCs. This pattern remained absent in control samples and was significantly associated with higher IgM peaks (p = 6.10-5 ) and MYD88 mutations (p = 10-3 ) in both WM and MGUS cases,” the researchers concluded.

Gayet M, Leymarie V, Derouault P, et al. Flow cytometry detection of CD138 expression continuum between monotypic B and plasma cells is associated with both high IgM peak levels and MYD88 mutation and contributes to diagnosis of Waldenström macroglobulinemia. Cytometry B Clin Cytom. 2022 Jan;102(1):62-69.

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