Medline ® Abstract for Reference 26
of 'Epidemiology, pathogenesis, clinical manifestations, and diagnosis of Waldenström macroglobulinemia'
The cellular origin and malignant transformation of Waldenström macroglobulinemia.
Paiva B, Corchete LA, Vidriales MB, García-Sanz R, Perez JJ, Aires-Mejia I, Sanchez ML, Barcena P, Alignani D, Jimenez C, Sarasquete ME, Mateos MV, Ocio EM, Puig N, Escalante F, Hernández J, Cuello R, García de Coca A, Sierra M, Montes MC, González-López TJ, Galende J, Bárez A, Alonso J, Pardal E, Orfao A, Gutierrez NC, San Miguel JF
Blood. 2015 Apr;125(15):2370-80. Epub 2015 Feb 5.
Although information about the molecular pathogenesis of Waldenström macroglobulinemia (WM) has significantly advanced, the precise cell of origin and the mechanisms behind WM transformation from immunoglobulin-M (IgM) monoclonal gammopathy of undetermined significance (MGUS) remain undetermined. Here, we undertook an integrative phenotypic, molecular, and genomic approach to study clonal B cells from newly diagnosed patients with IgM MGUS (n = 22), smoldering (n = 16), and symptomatic WM (n = 11). Through principal component analysis of multidimensional flow cytometry data, we demonstrated highly overlapping phenotypic profiles for clonal B cells from IgM MGUS, smoldering, and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between fluorescence-activated cell sorter-sorted clonal B cells from the 3 disease groups. Interestingly, the transcriptome of the Waldenström B-cell clone was highly different than that of normal CD25(-)CD22(+) B cells, whereas significantly less genes were differentially expressed and specific WM pathways normalized once the transcriptome of the Waldenström B-cell clone was compared with its normal phenotypic (CD25(+)CD22(+low)) B-cell counterpart. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23]progressively increased from IgM MGUS and smoldering WM vs symptomatic WM (18% vs 20% and 73%, respectively; P = .008), suggesting a multistep transformation of clonal B cells that, albeit benign (ie, IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström clone.
Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain;