Detalle Publicación

The cellular origin and malignant transformation of Waldenström macroglobulinemia

Autores: Paiva, Bruno; Corchete, L. A.; Vidriales, M. B.; Garcia-Sanz, R.; Perez, J. J.; Aires-Mejia, I.; Sanchez, M. L.; Barcena, P.; Alignani, D.; Jimenez, C.; Sarasquete, M. E.; Mateos, M. V.; Ocio, E. M.; Puig, N.; Escalante, F.; Hernandez, J.; Cuello, R.; Garcia de Coca, A.; Sierra, M.; Montes, M. C.; Gonzalez-Lopez, T. J.; Galende, J.; Barez, A.; Alonso, J.; Pardal, E.; Orfao, A.; Gutierrez, N. C.; San Miguel Izquierdo, Jesús
Título de la revista: BLOOD
ISSN: 0006-4971
Volumen: 125
Número: 15
Páginas: 2370 - 2380
Fecha de publicación: 2015
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 c